https://www.explorationpub.com/Journals/en Most Recent Articles : Exploration of Neuroscience. en-us Tue, 26 May 2026 23:47:47 GMT https://www.explorationpub.com/Journals/en/Article/10061 Not applicable. Editorial Sat, 02 Apr 2022 00:00:00 GMT Dirk M.Hermann, Sat, 02 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10061 https://www.explorationpub.com/Journals/en/Article/10062 All living organisms exhibit circadian rhythms. Humans show circadian rhythm of the different physiological functions such as sleep-wake cycle, core body temperature, feeding behavior, metabolic activity, heart rate variability, hormone secretion, and others. The hypothalamic suprachiasmatic nucleus (SCN) acts as a primary circadian pacemaker. Peripheral tissues have an endogenous circadian clock; however, SCN synchronizes the circadian activity of the peripheral clocks. The retinohypothalamic tract (RHT) from retinal ganglionic cells carries the photic signal into the SCN that regulates the rhythmic expression of the core clock genes through the feedback loop. At the output level, the SCN connects with the pineal gland and the peripheral tissues with the help of neuroendocrine mediators. Disruption of circadian clock functions is detrimental to health. Shift work, night work, chronic or acute jet lag, and light-at-night have adverse effects on circadian functions. Misalignment of circadian rhythm alters the expression of core clock genes, leading to deregulation of cellular activity and metabolic functions. Circadian rhythm dysfunction causes many pathologic conditions, including sleep disorders, cardiovascular problems, metabolic dysfunction, infertility, poor physical performance, as well as cancer. The present work has reviewed the relationship between circadian clock dysfunction and impaired physiological activities. Review Fri, 30 Sep 2022 00:00:00 GMT SaptadipSamanta, Sk AsifAli, Fri, 30 Sep 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10062 https://www.explorationpub.com/Journals/en/Article/10063 Neuregulins (NRGs) and their cognate ErbB receptors (ErbB2–ErbB4) constitute a vast group of proteins encoded by six different genes (NRG1–6) and many isoforms with critical roles in the development and functioning of the nervous system. NRGs are known to regulate important processes in the nervous system like neural development, neuronal differentiation, neurite outgrowth, and specification. These factors are involved in the regulation of neurotransmission pathways and the modulation of several forms of synaptic plasticity. Due to NRGs’ role in synaptic plasticity, defects in their normal functioning are translated into altered signaling networks, which have been linked to susceptibility to developing psychiatric disorders like schizophrenia (SZ), autism, depression, and bipolar disorders. Additionally, deviation of the NRG normal functioning is involved in neurological diseases like Alzheimer’s and Parkinson’s disease. Contrastingly, NRG/ErbB signaling is also involved in the recovery after traumatic brain injuries (e.g., ischemic stroke). The NRG/ErbB signaling complex is highly unusual because the ligands (mainly NRG1–NRG3, with their multiple isoforms) and receptors (ErbB2–ErbB4) can orchestrate vast signaling complexes, with a wide reach within the processes that govern the development and appropriate function of the nervous system. This may explain why NRGs and ErbB receptor genes have been linked to complex brain disorders, like SZ. This review, are discussed important aspects of NRG and their relevance for nervous system functioning, including 1) subcellular localization, 2) signaling pathways involved in neuronal functions, 3) effect on neurite development and synapse formation, 4) modulation of some mechanisms of synaptic plasticity [long-term potentiation (LTP), depotentiation, long-term depression (LTD)] and 5) roles of NRGs in some neurological diseases. This review intends to present a summary of the main findings about this family of proteins, which might position them as one of the master regulators of brain functioning. Review Fri, 30 Sep 2022 00:00:00 GMT MarinesLongart, ChristianCalderón, ManuelGonzález, María ElenaGrela, Juan CarlosMartínez, Fri, 30 Sep 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10063 https://www.explorationpub.com/Journals/en/Article/10064 This brief statement describes some recent achievements of neuropathological research, with the focus on Alzheimer’s and other age-related diseases, neurodegenerative disorders (tauopathies, synucleinopathies), multimorbidity of the aged brain, multiple sclerosis (MS), and other neuroinflammatory disorders, including central nervous system involvement by coronavirus disease 2019 (COVID-19), as well as new developments in neurovascular diseases, neurooncology, and myopathies. Although neuropathology, using modern technologies, such as cryo-electron microscopy, proteomic and experimental methods, has helped to increase diagnostic accuracy and provided insight into the pathogenesis of many neurological disorders, future studies in co-operation with clinical and other neurosciences should overcome the challenges of disease-influencing therapeutic approaches. Perspective Fri, 30 Sep 2022 00:00:00 GMT Kurt A.Jellinger, Fri, 30 Sep 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10064 https://www.explorationpub.com/Journals/en/Article/10065 Ischemic stroke is a highly prevalent condition that frequently results in life-long disability and death. Considerable efforts have been made to establish treatments that prevent secondary ischemic damage and promote stroke recovery. Until now, the recanalization of occluded blood vessels via thrombolysis and thrombectomy, although highly potent, remains the only treatment in humans that enhances stroke outcome. Small extracellular vesicles are non-replicating, nano-sized (70–150 nm) lipid bilayer-enclosed vesicles, which have shown remarkable biological activities in various physiological and pathophysiological contexts. When administered post-stroke, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) induce neuroprotection, promote brain remodeling and plasticity, and enhance neurological recovery in rodents and non-human primates via mechanisms that involve immunomodulation and anti-inflammation. In this review, experimental studies on the therapeutic actions of MSC-EVs in animal stroke models are summarized and perspectives for clinical translation are outlined. Review Sun, 09 Oct 2022 00:00:00 GMT ChenWang, BerndGiebel, Dirk M.Hermann, Sun, 09 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10065 https://www.explorationpub.com/Journals/en/Article/100697 Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia, characterized by cognitive decline in later years of life. Among various hypotheses explaining AD pathology, the cholinergic hypothesis is one of the most studied. Though there are Food and Drug Administration (FDA) approved drugs (donepezil, galantamine, rivastigmine and tacrine) for AD treatment, their adverse effects make it urgent to develop new drugs with minimal side effects. This review focuses on the acetylcholinesterase (AChE) inhibitory potential of plant extracts and phytochemicals that could aid in preventing and mitigating AD. From the literature search, extracts of 28 species were found to have strong inhibition against AChE, with IC50 values ranging from 0.08 μg/mL to 10.0 μg/mL. The highest number of species with AChE inhibition belongs to the Amaryllidacea family, followed by Fabaceae, Lycopodiaceae, Amaranthaceae and Anacardiaceae. Several phytochemicals, including alkaloids, terpenoids and phenolics, show a multitarget approach in AD therapy, exhibiting more than one of the following activities such as inhibition of AChE, butyrylcholinesterase (BuChE), MAO-A, beta site amyloid precursor protein cleaving enzyme 1 (BACE-1), β-amyloid (Aβ) aggregation, tau phosphorylation, and an ability to cross blood-brain barrier (BBB). With a multitarget approach and minimal side effects, they could revolutionise the treatment of AD. Many phytochemicals and their derivatives are under clinical and pre-clinical trials, potentially serving as prospective therapeutic drug candidates for treating AD. This review briefly discusses the findings and advances in knowledge about plant-derived bioactive compounds as potential new drugs acting as AChE inhibitors. Review Fri, 20 Jun 2025 00:00:00 GMT DeepaA V, DennisThomas T, Fri, 20 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100697 https://www.explorationpub.com/Journals/en/Article/10066 The therapy of many neurological disorders has advanced markedly during recent decades. Not so for neurodegenerative disorders. Early detection, deep individual genotyping and phenotyping, and personalized therapies have been suggested as the way forward. However, we still do not know enough about the aetiology and molecular basics of these diseases. In fact, the term neurodegenerative disorder may be a misleading categorization that constitutes a major cognitive barrier against better characterization and understanding of these disorders. Therefore, we need to go back to the basics and employ novel, open-minded observational study protocols that combine very extensive and robust clinical, molecular and epidemiological data collection methods. Moreover, we need to reconsider our basic orientation towards these diseases to increase our chances of finding out what we are actually trying to care for and cure. Perspective Mon, 26 Dec 2022 00:00:00 GMT Jussi O. T.Sipilä, Mon, 26 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10066 https://www.explorationpub.com/Journals/en/Article/10067 Stroke is a leading cause of morbidity and mortality. The advent of mechanical thrombectomy has largely improved patient outcomes. This article reviews the features and outcomes associated with aspiration, stent retrievers, and combination catheters used in current practice. There is also a discussion on clinical considerations based on anatomical features and clot composition. The reperfusion grading scale and outcome metrics commonly used following thrombectomy when a patient is still in the hospital are reviewed. Lastly, there are proposed discharge and outpatient follow-up goals in caring for patients hospitalized for a stroke. Review Fri, 30 Dec 2022 00:00:00 GMT KevinPierre, CarlosPerez-Vega, AnnaFusco, BankoleOlowofela, RamiHatem, MohammedElyazeed, MohammedAzab, BrandonLucke-Wold, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10067 https://www.explorationpub.com/Journals/en/Article/10068 Exposure to stressful conditions plays a critical role in brain processes, including neural plasticity, synaptic transmission, and cognitive functions. Since memory-related brain regions, the hippocampus (Hip), the amygdala, and the prefrontal cortex, express high glucocorticoid receptors (GRs), these areas are the potential targets of stress hormones. Stress affects memory encoding, consolidation, and retrieval, which may depend on many factors such as the type, duration, the intensity of the stressor or the brain region. Here, this review mainly focused on the mechanisms involved in stress-induced memory impairment. Acute/chronic stress induces structural and functional changes in neurons and glial cells. Dendritic arborization, reduction of dendritic spine density, and alteration in glutamatergic-mediated synaptic transmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are mechanisms that stress affect long-term memory formation. Exposure to acute or chronic stress could interplay with multiple neurotransmitter signaling, modulating the neuronal circuits involved in memory impairment or state-dependent learning. Stress hormones also modulate the expression of microRNAs in the specific brain regions responsible for stress-induced behaviors. Because of expressing GRs in astrocytes and microglial cells, stress could affect the morphology, structure, and functions of these glial cells in memory-related brain regions. Astrocytes play a crucial role in stress-induced aversive or fear memory formation. Over-activation of the microglial cells enhances the release of inflammatory cytokines, which results in neuronal injury. Stress has a prominent role in cognitive decline to induces memory problems, particularly in older adults. Due to the issue’s importance, here the provided overview attempted to address the question of how stress alters neuronal epigenetic regulators, synaptic transmissions, and glial activity in the brain. Review Fri, 30 Dec 2022 00:00:00 GMT AmenehRezayof, MaryamSardari, ShivaHashemizadeh, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10068 https://www.explorationpub.com/Journals/en/Article/10069 Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment. Graphical abstract.Hereditary risk factors, genetic mutations, and imaging modalities are discussed in reference to astrocytoma staging and mechanism of growth. In terms of the treatment of astrocytomas, chemotherapy, radiation therapy, and strategic surgical interventions are discussed Review Thu, 23 Feb 2023 00:00:00 GMT MatthewWillman, JonathanWillman, JohnFigg, EmmaDioso, SaiSriram, BankoleOlowofela, KevinChacko, JairoHernandez, BrandonLucke-Wold, Thu, 23 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/10069 https://www.explorationpub.com/Journals/en/Article/100610 Aim: Stroke is one of the leading causes of death and disability worldwide. Plasma biomarkers have long been used to evaluate physiological or pathological processes and to make predictions about the outcome of stroke patients. The current systematic review is focused on genetic plasma biomarkers as a new potential prognostic indicator for post-stroke recovery. The aim of the present systematic review is to assess the potential of genetic plasma biomarkers associated with stroke to predict post-stroke recovery. Methods: The search strategy used PubMed and Web of Science databases to identified 166 studies that investigated genetic plasma biomarkers in patients with stroke between 2017 and 2021. However, only 21 of them met the inclusion criteria. Results: The identified genetic biomarkers can be divided into: (i) serum/plasma circular RNA (circRNA) associated with stroke onset or recurrence (5; 23.80%), (ii) genetic polymorphisms associated with the atherosclerotic process and stroke recurrence (6; 28.57%), (iii) serum/plasma long non-coding RNA (lncRNA) levels involved in immunity/inflammatory processes (4; 19.04%), (iv) marker of DNA methylation associated with stroke onset and outcome (3; 14.28%), and (v) proteins and pathways of stroke identified by serum/ plasma proteomics/genomics analysis (3; 14.28%). Conclusions: Overall, more than 100 potential biomarkers were found and the data suggest that combinations of plasma genetic biomarkers might be used as a better predictor for stroke. Systematic Review Mon, 27 Feb 2023 00:00:00 GMT Mihai AndreiRuscu, DaianaBurdusel, Andreea-MihaelaCercel, MadalinaAldea, Dirk M.Hermann, Israel FernandezCadenas, Thorsten R.Doeppner, RoxanaSurugiu, AurelPopa-Wagner, Mon, 27 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100610 https://www.explorationpub.com/Journals/en/Article/100611 Not applicable. Editorial Tue, 28 Feb 2023 00:00:00 GMT Dirk M.Hermann, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100611 https://www.explorationpub.com/Journals/en/Article/1006111 Alzheimer’s disease (AD) is a chronic neurodegenerative disorder with declining memory and cognitive impairment, largely mediated by extracellular amyloid-beta (Aβ). Although the amyloid cascade and tau protein hypotheses have long served as established frameworks for AD pathology, recent evidence suggests that long-term infections, particularly with Chlamydia pneumoniae (C. pneumoniae), may contribute to disease progression. A systematic search strategy was used to identify relevant literature using PubMed, Scopus, Google Scholar, and Web of Science. Keywords and Boolean operators such as “Chlamydia pneumoniae and Alzheimer’s disease,” “neuroinflammation,” “amyloid-beta,” and “tau protein” were applied, with filters for peer-reviewed articles, human and experimental studies, and publications from the past 25 years. Epidemiological and background data were supplemented by official sources, including the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). This review examines the potential relationship of C. pneumoniae infection with AD pathogenesis. Studies have identified DNA and antigens of C. pneumoniae in AD-infected brain regions, often co-localized within Aβ plaques and neurofibrillary tangles (NFTs). Proposed mechanisms of CNS invasion include olfactory, hematogenous, and immune cell-mediated routes, leading to persistent glial activation, neuroinflammation, altered amyloid precursor protein processing, and tau protein hyperphosphorylation. Experimental models support these associations, with infected animals developing AD-like pathology. Diagnostic challenges persist due to the limitations of PCR and immunohistochemistry, though advanced approaches such as next-generation sequencing and TSPO-PET imaging are emerging. Potential therapeutic approaches include antimicrobial and immunomodulatory strategies, although human trials have shown mixed results. While current evidence suggests a possible link, causality remains unproven. Future research must prioritize large-scale, longitudinal, and mechanistic studies to clarify these relationships. Establishing a definitive role for C. pneumoniae in AD pathogenesis could reshape current understanding of disease etiology and inform the development of novel preventive and therapeutic strategies. Review Tue, 23 Sep 2025 00:00:00 GMT Atif SalimKhatib, Afra WasamaIslam, Subair SabbarAhmed, Syeda FatimaZehra, DaniyaTasnim, Tue, 23 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006111 https://www.explorationpub.com/Journals/en/Article/100612 Aim: Microglial activation is increasingly recognised as a factor in the progression of Alzheimer’s disease (AD) and may be modified by systemic inflammatory signals including serum tumour necrosis factor (TNF)-α. The aim was to investigate whether blockade of peripheral TNF-α with peripheral inhibitors such as etanercept reduces microglial activation in prodromal AD. Methods: A one-year, multi-centre, phase 2, double-blind randomised placebo-controlled trial (RPCT) was performed, to assess the effect of weekly 50 mg s.c. etanercept in amyloid positive mild cognitive impaired participants on the change in microglial activation as measured by [11C](R)-PK11195 positron emission tomography (PET). Secondary objectives were to ascertain the change in cortical amyloid load on PET and the change in the Montreal Cognitive Assessment (MoCA). Results: Forty-four subjects consented to the study. Twenty-eight subjects failed screening including six subjects who were amyloid negative on visual read of the AmyvidTM PET scans. Thirteen of sixteen subjects with mild cognitive impairment (MCI) due to AD completed the baseline [11C](R)-PK11195 PET scan and were randomised to either placebo or etanercept. Three patients who consented were not able to complete screening due to early termination of the study following delays in study commencement. [11C](R)-PK11195 binding potential (BP) at baseline showed an almost global increase in MCI patients as compared to age-matched controls. Compliance to medication was high over the twelve-month trial period with etanercept being well tolerated. The study did not achieve statistical power to show a significant effect of etanercept over 52 weeks in the limited number of patients with MCI on microglial activation as measured by [11C](R)-PK11195 PET. Overall uptake of florbetapir in the follow up (FU) scans remained stable. The study was not powered to show statistical differences in psychometric ratings between groups. Conclusions: This study did not show evidence that treatment with etanercept over one year would modulate microglial activation in amyloid positive MCI patients (EudraCT identifier: 2015-002145-63, https://www.clinicaltrialsregister.eu; International Standard Randomised Controlled Trial Number identifier: ISRCTN12472821, https://www.isrctn.com). Original Article Mon, 27 Mar 2023 00:00:00 GMT AlexanderGerhard, RichardSharples, TsepoGoerttler, KathrynMcDonald, EszterVisi, RainerHinz, FedericoTurkheimer, IsabelLewzey, KarlHerholz, Andreas H.Jacobs, CliveHolmes, Mon, 27 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100612 https://www.explorationpub.com/Journals/en/Article/100613 Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects. Review Fri, 21 Apr 2023 00:00:00 GMT YuriZilberter, TanyaZilberter, Fri, 21 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100613 https://www.explorationpub.com/Journals/en/Article/100614 Neuroinflammation plays a key role in the pathogenesis of post-cardiac arrest (CA) brain injury. Innate immune cells sense a variety of danger signals through pattern-recognition receptors and evoke rapidly after ischemic challenge, triggering inflammatory responses and amplifying brain damage. A programmed cell death (PCD) pathway is activated after ischemic and/or inflammatory stimuli, leading to the elimination of the damaged cells. However, PCD also regulates inflammatory responses flexibly. The present review aimed to summarize the mechanisms of inflammatory responses, including the biology of immune cells, the innate immune recognition that initiates the inflammation, and the immunomodulatory effects of PCD following CA. Promising therapeutic approaches of targeting inflammatory responses to alleviate brain injury and improve neurological outcomes after CA are also reviewed. Review Wed, 26 Apr 2023 00:00:00 GMT YuzhenZhang, ZhentongLi, KunxueZhang, YuanChang, JiancongChen, MuradAl-Nusaif, SuyuePan, KaibinHuang, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100614 https://www.explorationpub.com/Journals/en/Article/100673 Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces oxidative stress through free radical scavenging, activation of antioxidant enzymes, and stabilization of mitochondrial function. It also inhibits neuroinflammation through modulation of key signaling pathways. It suppresses amyloid-beta aggregation in Alzheimer’s and alpha-synuclein fibrillation in Parkinson’s, thus attenuating toxic protein accumulation. Its activity in the induction of autophagy and promotion of synaptic plasticity supports neuronal survival and function. However, low bioavailability and metabolic instability hinder its translation into the clinic. Strategies including nanoparticle encapsulation, structural modifications, and combination therapies are being explored to overcome these challenges. Future research could establish epigallocatechin gallate as a viable candidate for managing neurodegenerative disorders. Review Tue, 25 Feb 2025 00:00:00 GMT NehaKamboj, SanyaSharma, RahulKumar, Tue, 25 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100673 https://www.explorationpub.com/Journals/en/Article/100615 For more than a decade now, research studies, proof of concept work, and clinical trials have endeavored to understand how mesenchymal stem cells might be used to help protect, repair, and/or regenerate damaged brain tissue following stroke. To date, the majority of studies have not demonstrated significant improvements in either morbidity or medium-long-term outcome, although safety has been relatively well proven. Limitations are likely to be linked to the pathobiological complexity and seriousness of stroke tissue damage, low efficacy of treatment, and short half-life of bio-active proteins released by stem cells. This article will highlight the heterogeneity and limitation of completed studies and the current status of ongoing work. At the same time, the potential of other combinational type treatments, such as drug-loading and targeting, and the use of hydrogels is discussed. Perspective Wed, 28 Jun 2023 00:00:00 GMT YleniaPastorello, MarkSlevin, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100615 https://www.explorationpub.com/Journals/en/Article/100616 Globally, the incidence of Parkinson’s disease (PD) is increasing faster than other neurodegenerative disorders. Neuropathologically, PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta due to the accumulation of aggregates of misfolded α-synuclein (α-Syn) in the cytoplasm of these neurons, forming Lewy bodies. Extracellular vesicles (EVs) are associated with the spread of α-Syn to different brain areas. However, at the same time that these EVs contribute to the pathophysiology of PD, they can also be explored as therapeutic, serving as a vehicle to deliver specific molecules, since these vesicles can easily cross the blood-brain barrier. Thus, this review summarizes the recent progress in EVs as a therapeutic strategy for PD, focusing on their delivery to the brain, and discusses the potential challenges and future directions in this field. Review Fri, 30 Jun 2023 00:00:00 GMT Michelli RamiresTeixeira, Anderson LucasAlievi, Vitor Rodriguesda Costa, João RafaelDias Pinto, Rodrigo PinheiroAraldi, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100616 https://www.explorationpub.com/Journals/en/Article/100617 Earth’s rotation generates the basic circadian rhythm of day and night to which all living organisms must adapt to survive. In mammals, this happens thanks to a central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and to peripheral clock genes at the cellular level. The main environmental cue capable of synchronizing such clocks is light sensed by retinal ganglion cells signaling through a complex nervous pathway to the pineal gland which ultimately regulates melatonin synthesis that occurs during the night, darkness hours in all mammals. The central clock synchronized by melatonin drives the circadian oscillation of the sympathetic nervous system (SNS) adrenergic activity which in turn controls glucocorticoid production in the adrenal glands. These oscillations are integrated with peripheral cellular clocks by still not completely understood mechanisms and drive the homeostatic control of activity-rest (sleep) cycles, cardiovascular activity, body temperature, and immune-hematopoietic functions. The neuronal and hormonal mechanisms governing the circadian oscillation of hematopoiesis and immunity will be addressed in this review focusing on those offering therapeutic perspectives. Review Fri, 30 Jun 2023 00:00:00 GMT GeorgesMaestroni, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100617 https://www.explorationpub.com/Journals/en/Article/100618 The gut microbiota and dysbiosis have been implicated in various metabolic diseases and gastrointestinal disorders. Recently, there has been growing evidence suggesting the influence of gut microbiota on neurological disorders, including autism. Although the number of children diagnosed with autism is increasing, the exact cause of the disease remains unknown. Numerous factors, such as genetics, environment, and diet, appear to contribute to its onset. Nevertheless, a degree of general consensus exists regarding the notion that the disease’s progression likely demands the participation of multiple factors. Among the potential causes, the role of the microbiota is particularly intriguing. The gut and brain have extensive connections, with a significant number of neuronal cells in the gut, and autism is often associated with gastrointestinal issues. In this review, the most recent information available on autism and microbiota has been analyzed. Findings of this study indicate that: (1) the microbiota is clearly altered in individuals with autism spectrum disorder (ASD); (2) microbiota transplantation appears to be effective in reducing the severity of autism symptoms; (3) while the microbiota is not solely responsible for the onset of autism, it likely plays a significant role. Considering all the available information, it is suggested that modifying the gut microbiota may have a positive impact on individuals with autism. This opens up possibilities for the use of pre- or probiotics in the treatment of children with ASD, as well as the potential use of fecal microbiota transfer. Review Thu, 31 Aug 2023 00:00:00 GMT JeanDemarquoy, HaifaOthman, CarolineDemarquoy, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100618 https://www.explorationpub.com/Journals/en/Article/100619 Several bare metals, self-expanding stents have been approved by the Food and Drug Administration (FDA) to treat carotid stenosis, but no covered stents have been particularly examined or approved for carotid or cerebrovascular applications. Nonetheless, there are a number of potentially useful applications for covered stents in the brachiocephalic, carotid, and even intracranial arteries. As with currently accepted applications for bare metal carotid stents, the use of covered stents in carotid arteries has been reserved for patients who are at high risk for complications with open surgical management of their specific problem. The present case report emphasizes the safety and efficacy of covered stent in complex carotid artery reconstruction entailing stenosis and aneurysmal dilatation and through light on its impact on minimizing the risk of ischemic complications associated with endovascular or surgical carotid sacrifice. Case Report Thu, 31 Aug 2023 00:00:00 GMT MosaadSoliman, KhaledMowafy, Mostafa AbdElgwad, RosanSoliman, ReemSoliman, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100619 https://www.explorationpub.com/Journals/en/Article/100620 Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided. Review Fri, 01 Sep 2023 00:00:00 GMT Hans-KlausGoischke, Fri, 01 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100620 https://www.explorationpub.com/Journals/en/Article/100621 Brain development, a complex process, consisting of several phases, starting as early as two weeks after conception, and continuing through childhood till early adolescence, is crucial for the development of properly functioning body systems, behavioral traits, and neurocognitive abilities. Infancy and childhood are recognized as important periods for initial brain formation, however in later stages of life, such as childhood and adulthood, experiences, together with environmental exposures, can still influence brain physiology. The developing brain is particularly susceptible to epigenetic changes with many factors being proposed as modifiers by directly impacting DNA methylation as well as histone and chromatin modifications within genes implicated in development. These factors include: maternal stress and diet, exposure to pollutants, sleep quality, as well as dietary habits. Evidence indicates exposures to environmental threats can lead to inappropriate neurological, metabolic, and endocrine functioning often mediated by epigenetic mechanisms with symptoms manifesting themselves as early as childhood or in later stages of life. Therefore, the main aim of this review is to evaluate the current studies focused on negative environmental exposures and their consequences on the developing brain directed by epigenetic mechanisms. Review Thu, 28 Sep 2023 00:00:00 GMT MayaKomar-Fletcher, JuliaWojas, MariaRutkowska, GabrielaRaczyńska, AnielaNowacka, Joanna MichalinaJurek, Thu, 28 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100621 https://www.explorationpub.com/Journals/en/Article/100622 Life is the highest form of adaptation to the environment which is based on energy metabolism. To maintain life, the neuromuscular system must constantly interact with the environment. The striatal muscles are the main energy consumer and their access to energy fuel is mainly limited by the brain’s needs. In the state of wakefulness, the brain must continuously process streams of sensory signals and respond to them with motor actions. At the same time, the brain to be efficient must memorize the sensory-movement relationships. Brain memory networking requires additional energy allocation, and due to limited systemic energy resources, the processes of memorization are completed during the sleep phase when the inactive muscular system allows allocating the energy fuel to the brain functions such as memory trace formation and the removal of the activity-dependent waste products. Both physiological processes can be completed during sleep only, and consequently, chronic sleep disorder leads to pathological changes in brain functioning and escalation of neurodegenerative processes. Consequently, sleep disorders become the main cause of dementia which is the prodrome of Alzheimer’s disease. Review Mon, 09 Oct 2023 00:00:00 GMT Janusz WiesławBłaszczyk, Mon, 09 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100622 https://www.explorationpub.com/Journals/en/Article/100623 As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient’s risk for and experience of dementia. Review Mon, 16 Oct 2023 00:00:00 GMT Caroline GraceDavidson, Samuel JoelWoodford, ShreyaMathur, Daisy BrigitteValle, DevonFoster, IvelinaKioutchoukova, ArmanMahmood, BrandonLucke-Wold, Mon, 16 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100623 https://www.explorationpub.com/Journals/en/Article/100624 Aim: Apolipoprotein E (ApoE) isoforms, especially the ApoE4 isoform, are genetic risk factors for Alzheimer’s disease (AD). Moreover, the APOE ε4 haplotype has a dose-dependent association with an increased risk of amyloid-related imaging abnormalities (ARIA) in individuals receiving disease-modifying therapy for AD. Therefore, the importance of APOE genotyping or proteotyping has been highlighted. Here, the authors developed fully automated chemiluminescence enzyme-immunoassay kit for ApoE4 and Pan-ApoE, and evaluated their diagnostic concordance with the APOE genotyping. Methods: One hundred seventy-eight specimens were analyzed using the Lumipulse® G ApoE4 and Pan-ApoE for the ApoE proteotype and evaluated its diagnostic concordance with the APOE genotype. Results: The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and the polymorphism could be classified clearly by the ratio of ApoE4 and Pan-ApoE amount in plasma. Conclusions: The combination of Pan-ApoE and ApoE4-specific chemiluminescent enzyme immunoassay (CLEIA) assay is useful for predicting APOE ε4 allele status. Original Article Mon, 16 Oct 2023 00:00:00 GMT TatsushiYuri, RosinaDegrieck, DagmaraMinczakiewicz, HideoSato, JoKamada, TakuyaNakazawa, InaVandenbroucke, KatsumiAoyagi, HisashiNojima, Mon, 16 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100624 https://www.explorationpub.com/Journals/en/Article/100625 The two mainstays of therapy for refractory epilepsy are medication and surgery. Child behavioral and cognitive aspects of epilepsy can be improved by using a specialized dietary regimen such as the ketogenic diet (KD). The purpose of this review is to expand our understanding of KD as a nutritional therapy for children with refractory epilepsy and to provide insight into the physiological aspects of its efficacy as an alternative to anti-seizure medication. Either directly or indirectly, ketones, glucose restriction, and polyunsaturated fatty acids regulate epileptic seizures. For KD to be effective, all three of these components must be present, even though the exact mechanism is unknown. Increasing gamma-aminobutyric acid, mitochondrial biogenesis, and oxidative phosphorylation levels can also serve as a means of promoting stable synaptic function while also decreasing neural activity and excitability. Most side effects of KD are caused by mild metabolic abnormalities such as acidosis, hyperuricemia, hypercholesterolemia, hypocalcemia, and hypomagnesemia. Since medium-chain triglycerides (MCTs) produce more ketones per calorie than long-chain triglycerides, individuals who consume MCTs can consume more carbohydrates and protein. This review demonstrated that KD therapy led to positive outcomes for patients with refractory epilepsy. Further study is needed to evaluate whether less restrictive and easier-to-follow diets, such as the modified Atkins diet and MCT diets, have a similar effect on seizure treatment as the standard KD. Mini Review Tue, 31 Oct 2023 00:00:00 GMT SrilaxmiVityala, Krishna PriyaKanteti, Haseeb MannanAbdul, YethindraVityala, UjwalaDamineni, ShivuduBellam, Jaya BhargaviPaladugu, SwathiNenavath, Tue, 31 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100625 https://www.explorationpub.com/Journals/en/Article/100626 Epilepsy, a prevalent neurological disorder, is characterized by chronic seizures resulting from abnormal electrical activity in the brain. Adequate medical treatment allows roughly 70% of patients to enjoy a seizure-free life. However, throughout history, epilepsy has acquired diverse interpretations due to the experienced seizures, transforming the condition from a clinical issue into a social stigma. Therefore, the aim of this review study is to review stigma and psychosocial problems in patients with epilepsy (PwE). For this reason, this study utilises sources from the last ten years and reports current data. As a result of the review, it was found that societal discrimination in PwE arises primarily from inadequate knowledge, misconceptions, and negative attitudes toward the condition. Other contributing factors were include patients’ lower levels of education and income, frequent seizures due to inadequate treatment, age at onset, duration of the disease, depressive symptoms, and lack of social support. Also, it was found that the stigma individuals with epilepsy face plays a pivotal role in exacerbating their psychosocial problems. Unfortunately, stigma and psychosocial challenges appear to be in a vicious circle, with an increase in one increasing the other. Stigmatized patients tended to isolate themselves from society, further increasing their likelihood of experiencing a depressive mood or psychiatric comorbidity. Consequently, individuals with epilepsy encounter difficulties in various domains such as marriage, work, education, and personal life. Considering these significant psychosocial burdens, it is essential to recognize that epilepsy surpasses its medical implications. Unfortunately, current efforts to reduce stigma remain insufficient, necessitating urgent and comprehensive measures to address this issue. Review Wed, 06 Dec 2023 00:00:00 GMT KubraYeni, Wed, 06 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100626 https://www.explorationpub.com/Journals/en/Article/100627 Aim: One of the main risk factors for an ischemic stroke is significant carotid artery stenosis, and extracranial severe carotid artery stenosis accounts for 20% of ischemic strokes. Prior to the development of carotid artery stenting (CAS), the only effective and reliable treatment for carotid artery stenosis was carotid endarterectomy (CEA). This study compares the results of CAS and CEA in patients with significant carotid artery stenosis. Methods: Between 2018 and 2022, hospital records of all patients who underwent carotid artery revascularization at the institution were retrospectively analyzed. Patients were divided into two groups depending on whether CEA or CAS was performed for carotid revascularization. Propensity score matching was performed to reduce bias by equating the baseline clinical characteristics of the groups. To compare 30-day, 1-year, and long-term outcomes, rates of transient ischemic attack (TIA), myocardial infarction, stroke, all-cause mortality, and composite endpoints were analyzed. Results: After PSM, 76 patients each in the CEA and CAS groups were compared. The mean age was 69.80 years ± 11.35 years and 121 (80%) were male. The patients were followed up for a mean of 33 months ± 6 months. The incidence of TIA in the perioperative period [9 (12%) vs. 4 (5%); P < 0.05], TIA and composite endpoint at 1-year period [11 (15%) vs. 2 (3%); P < 0.05 and 27 (36%) vs. 16 (21%); P < 0.05, respectively] were significantly higher in the CAS group than in the CEA group. No difference was observed between the groups in the long-term. Conclusions: There was no noticeable difference between the CEA and CAS groups in the examination of cases with severe carotid artery stenosis in terms of 1-month, and 1-year results (apart from TIA and composite endpoints), or long-term outcomes. Extracranial carotid artery stenosis can be treated safely and effectively also by CAS. Original Article Thu, 14 Dec 2023 00:00:00 GMT OğuzhanBirdal, Eyüp S.Çalık, ÜmitArslan, YavuzerKoza, UğurKaya, AbdurrahimÇolak, M. HakanTaş, Thu, 14 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100627 https://www.explorationpub.com/Journals/en/Article/100628 Neuropathic pain is an increasingly common disease affecting millions of individuals worldwide. Refractory pain poses a significant impact on patients’ quality of life, financial and economic stability, and social interaction. Numerous effective modalities for treatment of refractory neuropathic pain are presently available. Currently, many options provide symptomatic treatment but are associated with an unfavorable side effect profile and increased risk of addiction. The present investigation reviews current medical management for refractory neuropathic pain including the use of antidepressants, anticonvulsants, gabapentinoids and opioid therapy, as well as interventional pain procedures such as spinal cord stimulation (SCS) and intrathecal targeted drug delivery. While multidisciplinary management with lifestyle modification and pharmacologic regimens remains at the forefront of treating many of these patients, interventional modalities are growing in popularity and have been demonstrated to be highly efficacious. In this regard, continued understanding of the pathophysiology surrounding refractory neuropathic pain has led to the development of interventional procedures and better outcomes for patients suffering from refractory neuropathic pain. When and if patients fail conservative therapy, interventional techniques are desirable alternatives for pain management. SCS and intrathecal targeted drug delivery are important tools for the treatment of refractory neuropathic pain. In summary, treatment modalities for refractory neuropathic pain are evolving with demonstrated efficacy. This review aims to outline the efficacy of various interventional procedures for refractory neuropathic pain in comparison to traditional drug therapies. Review Fri, 22 Dec 2023 00:00:00 GMT Hannah G.Matejowsky, SaurabhKataria, Noah J.Spillers, Collyn C.O’Quin, SonnahBarrie, ShahabAhmadzadeh, SaharShekoohi, Alan D.Kaye, Fri, 22 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100628 https://www.explorationpub.com/Journals/en/Article/100629 The circadian rhythm is a critical system that governs an organism’s functions in alignment with the light-dark cycle. Melatonin release from the pineal gland plays a crucial role in regulating the internal clock of the body. Multiple neurotransmitter systems in the central nervous system are linked to the release of melatonin. In this review, the relationship between circadian rhythm, melatonin secretion and various neurotransmitter systems are mainly discussed. Serotonin regulates the circadian rhythm through projections from raphe nuclei. Agomelatine is an example of the synergistic interaction between melatonin and serotonin. Melatonergic agents and selective serotonin reuptake inhibitors also exert notable impacts on depression in concomitant use. Dopamine has an inhibitory effect on melatonin release, while melatonin also inhibits dopamine release. This should be taken into account when considering the use of melatonin in Parkinson’s disease. On the contrary, use of melatonin may offer therapeutic advantages for schizophrenia and tardive dyskinesia. The interaction between norepinephrine and melatonin exhibits diurnal variability, with norepinephrine promoting arousal and inhibiting daytime melatonin secretion. Melatonergic neurons also exert a specific protective influence on cholinergic neurons. Interaction between the histaminergic and melatonergic systems is significant, particularly in association with immunity, sleep, and circadian rhythm. Novel ligands with dual-acting properties, interacting with both the histaminergic and melatonergic systems are investigated. Currently, there is a limited number of approved melatonergic agents that primarily demonstrate positive effects in addressing insomnia and depression. However, there is considerable potential in studying new agents that target both the melatonergic and other neurotransmitter systems, which alleviate various conditions, including neurodegenerative diseases, dementia, autoimmune diseases, allergic diseases, epilepsy, and other neuropsychiatric disorders. The ongoing process of developing and evaluating new ligands selectively targeting the melatonergic system remains crucial in understanding the complex relationship between these systems. Review Fri, 22 Dec 2023 00:00:00 GMT UtkuAykan, Muhammed CihanGüvel, GökçenPaykal, CananUluoglu, Fri, 22 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100629 https://www.explorationpub.com/Journals/en/Article/100630 Neural disorders refer to conditions of the nervous system due to infection or degeneration of the neurons leading to either neurodegenerative disorder or neuropsychiatric disorder. Some such disorders of the nervous system include Parkinsons’s disease, depression, amnesia, dementia, Alzheimer’s disease, schizophrenia, cerebrovascular impairment, epilepsy, seizure disorders, etc. In conventional medical system, some medicines belonging to the class of psychodelic drugs, sedatives, neurotransmitters, neuro-stimulants, etc. are in extensive use. Unfortunately, most of these drugs either delay the progression of the neural disorder or leave the patient with prominent adverse side effects. Several potent bioactive compounds with neuroprotective potential have been reported from medicinal plants and some of them have been found to be highly effective. Belonging from natural sources, mostly, the plant derived compounds exhibit minimum or no cytotoxicity at a prescribed standardised dose against a particular health ailment. Many such phytocompounds from plant sources with potent neuroprotective activities have been in use in Ayurvedacharya, Unani, and Chinese medicine for ages. The compounds if isolated chemically, modified to make more potent neuroprotective derivatives and utilised to make highly effective neuroprotective pharmaceutical formulations with minimum side effects, may open new revolutionary doorways in neuropharmacology. In this review, it has been briefly discussed about the neuroprotective compounds isolated from certain indigenous plants of West Bengal, India, and their mechanism of action. Mini Review Tue, 26 Dec 2023 00:00:00 GMT SuvenduGhosh, Partha SarathiSingha, DebosreeGhosh, Tue, 26 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100630 https://www.explorationpub.com/Journals/en/Article/100631 Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments for cerebral tumors. It will focus on the current and, more importantly, developing hemangioblastoma treatments. Surgical resectioning and radiotherapy are effective treatment options for cerebral tumors, whereas chemotherapies are not commonly used due to their limited ability to penetrate the blood-brain barrier. Recent chemotherapies have shown promise, but further research is needed to determine the efficacy as a treatment for hemangioblastomas. New advances in brachytherapy and immunotherapy are considered promising treatment options for hemangioblastoma. This review aims to offer valuable insights into the latest developments in hemangioblastoma treatments. Review Fri, 29 Dec 2023 00:00:00 GMT ChaitanyaSanghadia, Melanie E.Martinez, MarisaMcNulty, EricRuss, MaxwellWoolridge, Dat ThanhCao, MarkoMicunovic, JefferyRoberts, JuanPerez, BrandonLucke-Wold, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100631 https://www.explorationpub.com/Journals/en/Article/100632 Bipolar disorder (BD) is a debilitating psychiatric disorder characterized by recurrent depression, mania, and hypomania episodes. The interaction of psychological, neuropsychological, and neurobiological factors (cognitive, behavioral, and emotional) is implicated in the development and persistence of BD. Accordingly, almost all investigators confirm that BD is the outcome of psychological and genetic interactions. Therefore, researchers should consider various factors in the psychopathology and psychotherapy of BD. This selective review first reviews research on these factors, then points to a variety of therapeutic methods for BD [interpersonal and social rhythm therapy (IPSRT), cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and family-focused therapy (FFT)], and finally suggested a new comprehensive integrated model for the assessment and therapy of BD. Review Fri, 29 Dec 2023 00:00:00 GMT BehroozAfshari, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100632 https://www.explorationpub.com/Journals/en/Article/100633 Receptor tyrosine kinases (RTKs) are known to perform versatile roles in disease landscapes, which determine the fate of the cell. Although much has been discussed from the perspective of proliferation, this review focuses on the impact of RTK-mediated signaling and its role in cytoskeletal degradation, the penultimate stage of cellular degeneration. In the case of degenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), age-related macular degeneration (AMD), and type 2 diabetes mellitus (T2DM), RTK signaling has been reported to be perturbed in several studies. The implications of downstream signaling via these receptors through canonical and noncanonical pathways alter the status of actin filaments that provide structural integrity to cells. Degenerative signaling leads to the altered status of rat sarcoma (Ras), Ras homologous (Rho), Ras-related C3 botulinum toxin substrate (Rac), and cell division control protein 42 (Cdc42), the best-characterized components of the cytoskeleton remodeling machinery. RTKs, along with their diverse adaptor partners and other membrane receptors, affect the functionality of Rho family guanosine triphosphate hydrolases (GTPases), which are discussed in this review. To conclude, this review focuses on therapeutic strategies targeting RTKs and Rho GTPase-mediated pathways that can be more effective due to their combined multifactorial impact on neurodegenerative cascades. Review Tue, 20 Feb 2024 00:00:00 GMT PriyankaSengupta, RussaDas, PiyaliMajumder, DebashisMukhopadhyay, Tue, 20 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100633 https://www.explorationpub.com/Journals/en/Article/100634 Proprioception provides important sensory feedback regarding the position of an animal’s body and limbs in space. This interacts with a central pattern generator responsible for rhythmic movement, to adapt locomotion to the demands that an animal’s environment places on it. The mechanisms by which this feedback is enabled are poorly understood, which belies its importance: dysfunctional proprioception is associated with movement disorder and improving it can help reduce the severity of symptoms. Similarly, proprioception is important for guiding accurate robotic movement and for understanding how sensory systems capture and process information to guide action selection. It is therefore important to interpret research that investigates mechanisms of proprioception, to ask: what type of information do proprioceptive sensors capture, and how do they capture it? Work in mammalian models has made important progress towards answering this question. So too, has research conducted Drosophila. Fruit fly proprioceptors are more accessible than mammalian equivalents and can be manipulated using a unique genetic toolkit, so experiments conducted in the invertebrate can make a significant contribution to overall understanding. It can be difficult, however, to relate work conducted in different models, to draw general conclusions about proprioception. This review, therefore, explores what research in the fruit fly has revealed about proprioceptor function, to highlight its potential translation to mammals. Specifically, the present text presents evidence that differential expression of mechanoelectrical transducers contributes to tuning of fly proprioceptors and suggests that the same mechanism may play a role in tuning mammalian proprioceptors. Review Wed, 21 Feb 2024 00:00:00 GMT IainHunter, Wed, 21 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100634 https://www.explorationpub.com/Journals/en/Article/100635 Aim: The ability of synthetic 1,4-naphthoquinones (1,4-NQs) to prevent adenosine triphosphate (ATP)-induced and purinergic P2X7 receptor (P2X7R) mediated inflammation in macrophage and neurodegeneration of neuronal cells in vitro was previously established. The aim of the present study was to investigate analgesic-like and anti-inflammatory activity of 1,4-NQs thioglucoside derivatives, compounds U-286 and U-548, in in vivo experiments. Methods: Spectrofluorimetry approach and YO-PRO-1 fluorescent dye uptake determination were applied to study the effect of 1,4-NQs upon ATP-induced P2X7R mediated macropore formation in mouse neuroblastoma Neuro-2a cells and macrophages RAW 264.7 cells. An acetic acid-induced writhing test, hot plate test, and carrageenan-induced paw edema test were used as an in vivo mouse models to study the ability of 1,4-NQs to inhibit pain and inflammation. In the in vivo experiments, compounds were administered to mice intraperitoneally at dosages of 0.1 mg/kg, 1.0 mg/kg and 10.0 mg/kg. A group of animals that received injections of sterile water was used as a control. Each dosage group and the control group consisted of 6 mice. Results: In the present work the analgesic-like and anti-inflammatory activity of 1,4-NQs, U-286 and U-548, was demonstrated. Compound U-548 showed a significant inhibitory effect in antinociceptive tests reducing the number of mouse writhings and eliminating the latent time of mouse hind paw licking, correspondingly. Selected compounds were able to almost completely reduce the size of carrageenan-induced paw edema 24 h after injection and had a potent anti-inflammatory activity. Observed effects were accompanied with aptitude of studied 1,4-NQs to inhibit the formation of purinergic P2X7R macropore associated with inflammation and nociceptive pain. Conclusions: The results obtained allow to consider compounds U-286 and U-548 and as a pharmacological basis for the development of new analgesic-like and anti-inflammatory drugs. Original Article Thu, 22 Feb 2024 00:00:00 GMT SergeiKozlovskiy, EvgenyPislyagin, EkaterinaMenchinskaya, EkaterinaChingizova, YuriSabutski, SergeyPolonik, IrinaAgafonova, DmitryAminin, Thu, 22 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100635 https://www.explorationpub.com/Journals/en/Article/100636 The ubiquity of circadian rhythms in living organisms has generally been accepted by researchers over the last century. Indeed, morphology and molecular biology of the circadian clock were described during the last fifty years. This main biological clock is located in the suprachiasmatic nucleus of the hypothalamus. This nucleus is connected with the retina by the retinohypothalamic tract. This way, light regulates the functioning of the biological clock and biological rhythms such as the sleep-wake cycle and other cyclic functions by releasing melatonin from the pineal body (PB) into the general circulation. Melatonin reaches the retina via the bloodstream as humoral feedback. More than a hundred years ago a reverse neuronal connection between the central nervous system and the retina was hypothesized. This so-called centrifugal visual or retinopetal system has been explored in detail in birds, but less information is available in mammals. In this work, the morphology and physiology of mammalian centrifugal visual pathways are reviewed. It is generally accepted that the centrifugal (retinopetal) fibers terminate mainly on the amacrine cells of the retina. Histaminergic fibers terminate on dopaminergic amacrine cells. Serotoninergic synapses were identified on ganglion cells. In addition, serotoninergic fibers were also associated with photoreceptor terminals. Luteinizing hormone releasing hormone fibers have been observed in birds, but not in mammalian retinas. In summary, based on the data available in the literature, it seems that the retinopetal system has a mandatory role in lower vertebrates, but a modulatory role in mammals. There is currently no adequate way to eliminate the centrifugal visual system that would better explain its true function. Review Fri, 23 Feb 2024 00:00:00 GMT ViktóriaVereczki, KatalinKöves, ÁgnesCsáki, Fri, 23 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100636 https://www.explorationpub.com/Journals/en/Article/100637 Stroke is among the leading causes of mortality and disability; therefore, it constitutes a relevant health problem. Cuban policosanol presents lipid-lowering, antiplatelet, antioxidant and vascular endothelium protective properties, all of which give it a comprehensive anti-atherosclerotic effect. This review is aimed to show, analyze and discuss the main preclinical and clinical evidence of the effects of Cuban policosanol on ischemic stroke. Preclinical studies evidenced the anti-ischemic effects of preventive and therapeutic oral treatment with Cuban policosanol in Mongolian gerbils with cerebral ischemia induced by unilateral and permanent ligation of a carotid artery, and in global cerebral ischemia induced by bilateral clamping and recirculation of both carotids; being similar or superior to other anti-ischemic agents. Also, combination therapy with aspirin produced greater anti-stroke efficacy compared with aspirin monotherapy, but being similar to policosanol plus atorvastatin combination. This anti-stroke effect was associated to a serum thromboxane A2 (TxA2) concentrations reduction and prostacyclin (PgI2) increase, leading to a favorable TxA2/PgI2 balance, and also to the malondialdehyde (MDA) and sulfhydryl groups (SHG, lipid peroxidation and protein oxidation markers, respectively) reduction. Cuban policosanol combined with aspirin (standard therapy) improved and benefited patients with prior ischemic stroke in terms of functional and neurological outcomes, in open-label studies and in randomized, double-blind, controlled studies. These beneficial effects on stroke patients were associated with antioxidant and antiplatelet effects of policosanol. Also, the combinations of Cuban policosanol plus aspirin and atorvastatin plus aspirin compared in a clinical study significantly and similarly improved the neurological recovery of patients with ischemic stroke. Cuban policosanol was safe and well tolerated, with no serious adverse events occurring during the trials. In conclusion, Cuban policosanol is a safe and effective natural drug for ischemic stroke treatment, which is supported by preclinical and clinical evidences. Review Mon, 26 Feb 2024 00:00:00 GMT VivianMolina Cuevas, AmbarOyarzábal Yera, Mon, 26 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100637 https://www.explorationpub.com/Journals/en/Article/100638 Pesticides are used to ensure the mass production and quality of foods, depending on the environment where they are grown. Trace amounts of pesticides are ingested through diet and high ratios of its components have been detected in humans. Neonicotinoid insecticides are nicotine analogs that disrupt neurons, induce neural excitation, and cause behavioral abnormalities and chronic toxicity. The herbicide glyphosate causes behavioral disorders due to abnormalities in the balance of intestinal microflora. These abnormalities can be found in the F2-generation and beyond. Glyphosate decreases the number and size of experimental animal fetuses, possibly through abnormal deoxyribonucleic acid methylation in parental germ cells, resulting in transgenerational toxicity. It also causes the death of dopamine neurons, which are believed to be involved in the development of Parkinson’s disease (PD). The intestinal microflora is considerably altered by ingesting pesticides used in crops. Lactic acid bacteria and some other intestinal bacteria have gut-regulating and immunomodulatory effects that have recently been implicated in neurological disorders, such as depression and dementia. Therefore, a healthy diet should be traced back to crops. An agriculture-medicine partnership linking “agriculture” and “preventive medicine” has recently been considered important based on the hypothesis that agriculture and health sectors should collaborate to create a healthy environment for producing healthy food. Although food considerations tend to focus on the functionality of vegetable and fruit components, that of environmental bacteria should also be considered. Review Sun, 07 Apr 2024 00:00:00 GMT TomomiKomura, MasaruYoshida, YoshikazuNishikawa, Sun, 07 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100638 https://www.explorationpub.com/Journals/en/Article/100639 Background: The main objective of the study was to carry out a systematic literature review to investigate the beneficial role of antioxidants in obesity and diabetes and the association of antioxidants in neuro-gliopathies and gut microbiome on antioxidant production and enteric nervous system (ENS) protection. Methods: A literature search was done electronically on 8 June 2022 in the databases Google Scholar, and PubMed, reviewing all the articles published in English. There were no limitations for the study (region, or any time frame). The study included randomized controlled trials (RCTs) and observational studies on a human subject, primarily focusing on information such as a change in body weight, body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), fasting blood glucose level, glycated haemoglobin (HbA1c), and other parameters that connected with diabetes and obesity. The search was also conducted for neuro-gliopathies and gut microbiome. Results: The beginning database search picked out a total of 2,428 articles, 1,310 in PubMed, 876 in Google Scholar, and 242 records from other sources. A total of 2,040 (total duplicates 388) was found after removing the duplicated articles, and after reading the title and abstracts were further decreased to 139 full-text articles. These 139 studies went for full-text analysis, which resulted in the exclusion of 123 studies and generated a final 16 articles included for systemic analysis. Discussion: This literature search of present studies shows the interconnection between antioxidant intake among obese and diabetes neuro-gliopathies. The findings indicate both obese and diabetic patients have a minimum content of antioxidants, especially carotenoids, retinol, ascorbic acid, tocopherol, magnesium, and zinc. While few research illustrated that ingestion of the abovementioned antioxidants was lowered among diabetes and obese subjects in contrast with their normal-weight population, this was not endorsed by every study. Systematic Review Mon, 08 Apr 2024 00:00:00 GMT LuxitaSharma, DhananjaySharma, Mon, 08 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100639 https://www.explorationpub.com/Journals/en/Article/100640 Brain metastasis is the most prevalent neurologic problem of systemic cancer and it can increase the mortality rate in patients with cancer. It occurs more in patients with lung cancer, breast cancer, and melanoma. There are several molecular mechanisms in cancer cell progression, invasion, and location in new places during brain metastasis. Significant interactions between cancer cells, the brain microenvironment, and the blood-brain barrier (BBB) play a major role in brain metastasis. This study will focus on molecular mechanisms that contribute to cancer metastasis into the brain and finding new treatments with molecular research. Treatment strategies in patients with brain metastasis include surgical resection, radiotherapy, and chemotherapy; however, the penetration of chemotherapy drugs beyond the BBB is limited. Studying molecular, cellular, and physical mechanisms in brain metastasis helps to improve new strategies in drug delivery across the BBB. There are significant impacts of ion channels in brain metastasis and cancer treatment failure. Targeting molecular mechanisms and ion channels in brain metastasis led to increasing the better response in these patients. In this way, nano-drugs have caused a revolution in effective targeting and drug delivery in cancer treatment. This review describes the advances to facilitate the penetration of drugs in the BBB by using nano-drugs especially those that are targeting ion channels. Review Wed, 10 Apr 2024 00:00:00 GMT Zohreh KhosraviDehaghi, Wed, 10 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100640 https://www.explorationpub.com/Journals/en/Article/100643 Epileptic seizures are prevalent in people with brain vascular abnormalities like arteriovenous malformations (AVMs) and cavernous malformations, greatly affecting their quality of life. The connection between intracranial vascular abnormalities and epilepsy is still under debate. Therefore, investigating epilepsy in individuals with AVMs is a crucial and current research area. This review presents a comprehensive examination of recent developments in epilepsy among individuals with brain AVMs. The authors conducted a detailed analysis of the natural progression, epidemiology, diagnostic methods, therapeutic approaches, and post-treatment outcomes for individuals with epilepsy associated with AVMs. Review Mon, 13 May 2024 00:00:00 GMT JohamChoque-Velasquez, UrielTagle-Vega, Francisco de JesúsGarcía-Mendoza, EmiliaMachado-Musri, MauricioGuerrero-Ocampo, Alder FernandoValenzuela-Rangel, Mon, 13 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100643 https://www.explorationpub.com/Journals/en/Article/100641 Aim: The aim of this paper is to discuss the main features and first outcomes of a therapeutic platform proposed to implement a public health therapeutic service for patients suffering refractory epilepsy. Methods: The proposal is a three-layer system composed by a new portable therapy device and two software applications. The therapy is transcutaneous electrical vagus nerve stimulation, known as tVNS. The primary layer is composed of tVNS devices, configured for each patient according to the instructions provided by the specialists. The middle layer is named “hospital data collector” (HDC), its main tasks are the patient enrollment, the device setup, and the database maintenance to store therapeutic parameters and session events together with the information cited previously. Each hospital center runs a HDC that is connected to a cloud application named “system cloud application (SCA)” which concentrates all the data supplied by the HDCs. Artificial intelligence methods are integrated in the SCA to predict the treatment effectiveness for every new patient based on the accumulated knowledge from the enrolled previously. Results: A version of the proposed system is running at the Institute of Neurology and Neurosurgery. The sensitivity of the therapeutic device with the proposed treatment protocol reaches 83.33% in the 18-patient pilot trial carried out. Conclusions: The proposed approach seems a useful therapeutic tool based on the pilot trial outcomes. The developed device is comfortable and suitable for the intended use. The proposed system has created the essential conditions to feed and grow a knowledge, a basic element to predict the treatment effectiveness for each new patient. It is a promising option for a refractory epilepsy therapy service. Original Article Fri, 12 Apr 2024 00:00:00 GMT Rene IvanGonzalez-Fernandez, VicenteRio-Vazquez, Jorge GermanPerez-Blanco, ErnestoVelarde-Reyes, LianaPortela-Hernandez, AiselSantos-Santos, JoelGutierrez-Gil, Jose LuisHernandez-Caceres, Fri, 12 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100641 https://www.explorationpub.com/Journals/en/Article/100642 Major depressive disorder (MDD) is a common mental disorder associated with significant suffering and disability. Recent evidence has highlighted the role of the gut-brain axis in the pathogenesis of MDD. Enteric glial cells are a structurally and functionally diverse population that plays a key role in regulating enteric nervous function and maintaining intestinal mucosal integrity. These cells may be implicated in the origin of several digestive and extra-digestive disorders, known as enteric neuro-gliopathies (ENG). This paper reviews the evidence that MDD may also belong to the category of ENG. Animal models suggest that environmental adversity can lead to enteric glial dysfunction and depressive-like behaviors. Conditions that are highly comorbid with MDD, both intestinal and extra-intestinal, have been linked to enteric glial alterations. Peripheral blood markers linked to glial integrity and function are altered in patients with MDD, and certain treatments for MDD may have beneficial effects on enteric glial functioning. Though much of this evidence is indirect and provisional, it suggests that MDD may belong to the group of ENG. Further investigation of enteric glial functioning in MDD may yield valuable insights into the pathophysiology and treatment of this disorder. Review Mon, 29 Apr 2024 00:00:00 GMT Ravi PhilipRajkumar, Mon, 29 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100642 https://www.explorationpub.com/Journals/en/Article/100645 Aim: The aim of this work was to study the effects of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) on inflammation-impaired cognitive functions and the brain of mice. Methods: Young mice (~3-month-old) and aged mice (~18-month-old) were injected with bacterial lipopolysaccharide (LPS) and obtained intravenously donor 106 human umbilical cord MSCs, EVs isolated from a similar amount of MSCs or conditioned medium (CM) of MSCs. Subsequently, the mice were examined in behavioral tests and the mouse brains were analyzed for the levels of pro-inflammatory cytokines, α7 nicotinic acetylcholine receptors (α7 nAChRs) and amyloid beta 1-42 (Aβ1-42). Results: EVs prevented LPS-induced memory impairment in mice, whereas CM provided a weaker and temporal effect. Both EVs and MSCs injected once after regular injections of LPS stably improved memory of young mice. In contrast, both cells and EVs provided only transient effect in aged mice injected with LPS. The brains of aged LPS-treated mice contained elevated amounts of IL-1β and IL-6; both MSCs and EVs decreased them significantly. The brains of non-treated aged mice contained decreased levels of α7 nAChRs and increased levels of Aβ1-42 and α7-bound Aβ1-42 compared to the brains of young mice. LPS treatment decreased α7 nAChRs in both young and aged mice, while both MSCs and EVs restored them up to the control level. In young mice, LPS treatment increased the level of Aβ1-42 and α7-bound Aβ1-42, whereas MSCs and EVs decreased it. In contrast, neither LPS nor MSCs/EVs influenced the elevated level of Aβ1-42 but increased α7-bound Aβ1-42 in the brains of aged mice. Conclusions: Regenerative potential of MSCs and MSC-derived EVs is sufficient to support cognitive functions of LPS-treated young mice but is quite poor for aged animals, possibly, due to decreased levels of α7 nAChRs and accumulated Aβ1-42 in their brains. Original Article Wed, 12 Jun 2024 00:00:00 GMT OlenaLykhmus, OlenaKalashnyk, MarynaSkok, OlenaDeryabina, OlenaToporova, IaninaPokholenko, OksanaGorbatiuk, VitaliiKordium, Wed, 12 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100645 https://www.explorationpub.com/Journals/en/Article/100644 New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prompting a workup for epilepsy surgery. Because NORSE remains etiologically elusive in most cases, surgical evaluations are challenging, especially when the epileptogenic zone (EZ) is not easy to lateralize as can be seen in frontal lobe seizures. Lateralizing a frontal lobe EZ may be challenging due to bilateral synchrony from commissural connections through the corpus callosum and low spatiotemporal resolution of the scalp electroencephalography (EEG). We report a pediatric patient with NORSE presenting with focal impaired awareness seizures clustering into super refractory status epilepticus (SRSE). She required surgical intervention for the treatment of her seizures after failing therapeutic doses of antiseizure medications, anesthetic drips, immunomodulation with methylprednisolone, intravenous immunoglobulin and anakinra, and the ketogenic diet. Despite her semiology being focal, the seizures were not well lateralized on scalp EEG and during phase 2 stereo-EEG (sEEG). Anterior magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy (MRgLITT CC) was performed in a multistage surgical approach to successfully lateralize the EZ with a left-lateralized ictal pattern seen after reimplantation of sEEG electrodes. Our case suggests that minimally invasive MRgLITT CC can be successfully used to lateralize an EZ in frontal lobe epilepsy and that epilepsy surgery should be considered in patients with NORSE with SRSE. We also demonstrate that laser interstitial thermal therapy (LITT), while not always resulting in seizure freedom, can sufficiently disrupt a network to abort status epilepticus and lead to seizure improvements. Case Report Tue, 04 Jun 2024 00:00:00 GMT KabirSheikh, DerrylMiller, RobertBlake, LisaSmith, SusanConrad, DeborahSokol, MakramObeid, RupaRadhakrishnan, AnnaSchultheis, JeffreyRaskin, Tue, 04 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100644 https://www.explorationpub.com/Journals/en/Article/100646 Aim: The aim of this study was to validate a Chinese version of the painDETECT questionnaire (PD-Q) for the screening and assessment of neuropathic pain (NeP) in a Hong Kong Chinese population. Methods: The PD-Q was translated and cross-culturally adapted from the original German PD-Q, with forward and backward translation according to standard guidelines followed by cognitive debriefing, and finalized by an expert panel. A multicenter (6-site) observational study was conducted to evaluate the validity of the PD-Q. Patients aged 18 or above with medical conditions giving rise to either neuropathic or nociceptive pain (NoP) provided informed consent to participate in this study. Each patient was evaluated by at least two healthcare professionals for causes of pain, the visual analogue scale (VAS), numeric rating scale (NRS) and the PD-Q. Results: Hong Kong Chinese adults (n = 151) were given the clinical description of NeP (n = 93), NoP (n = 41), or mixed pain (n = 17). The mean age of study subjects was 58.5 years (age range: 26–90 years); 94 subjects (62.3%) were female. The mixed pain group was only analysed qualitatively, with validation based on the remaining 134 patients. Mean PD-Q scores for patients diagnosed with NeP and NoP were 19.9 [standard deviation (SD) = 6.4] and 12.5 (SD = 6.2) respectively. Receiver operating characteristic (ROC) curves were plotted for the upper/lower boundaries. The upper boundary was calculated on the basis of a neuropathic diagnosis and a nociceptive diagnosis. The cut-off point was > 18 (80% sensitivity, 60% specificity), and area under the ROC curve (AUC) was 0.67 (P < 0.001). The lower boundary was calculated on the basis of a nociceptive and a neuropathic diagnosis. The cut-off point was < 13 (90% sensitivity, 50% specificity), and AUC was 0.79 (P < 0.001). Conclusions: The PD-Q is a reliable and valid scale to determine neuropathic components of chronic pain in the Hong Kong Chinese population. Validation in a larger Chinese-speaking population worldwide is necessary. Original Article Fri, 14 Jun 2024 00:00:00 GMT HowanLeung, Josephine W.Y.Ip, Joseph M.K.Lam, Gavin K.W.Lee, Carina C.F.Li, RichardLi, VincentMok, Tak H.Tsoi, Chun P.Wong, Steven H.S.Wong, Chun M.Chang, RainerFreynhagen, Fri, 14 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100646 https://www.explorationpub.com/Journals/en/Article/100647 Neurological disorders including neurodegenerative disorders continue to pose significant therapeutic challenges. Triterpenoids, a diverse group of natural compounds found abundantly in plants, possess promising neuroprotective properties. This review aims to explore the potential of triterpenoids in mitigating neurodegeneration through various mechanisms, including antioxidant, anti-inflammatory, and anti-apoptotic activities. The neuroprotective potential of some notable triterpenoids, such as asiatic acid, asiaticoside, madecassoside, bacoside A, bacopaside I, ganoderic acids, and lucidenic acids are discussed in terms of their ability to modulate key pathways implicated in neurological disorders. Additionally, the potential therapeutic applications of triterpenoids in Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, spinal cord injury, and epilepsy are examined. Furthermore, the review also underlines the challenges for the development of triterpenoids as neuroprotective agents, including the need for further preclinical and clinical studies to elucidate their efficacy and safety for translation into clinical practice. Review Wed, 26 Jun 2024 00:00:00 GMT Apoorva A.Bankar, Vaishali P.Nagulwar, Nandkishor R.Kotagale, Nazma N.Inamdar, Wed, 26 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100647 https://www.explorationpub.com/Journals/en/Article/100648 Alzheimer’s disease (AD) is a major type of dementia and neurodegenerative disease, characterized by memory loss and cognitive decline. Over decades, significant efforts have been dedicated to finding its cause, pathogenic mechanisms, biomarkers for early detection, and clinical trials for its treatment. Earlier approved drugs mainly ameliorated the symptoms of AD, until recent years when two drugs targeting amyloid-beta (Aβ) protein were approved to slow down the progression of the disease. This review article encompasses the history of drug development in treating AD and clinical trials that failed and succeeded. Clinicaltrials.org website was systematically searched and screened for randomized controlled trials with results posted in the past 10 years. Among the 3,388 AD clinical trials, 211 interventional studies registered under AD have met eligibility. This review includes the interventional targets for drug discovery such as Aβ, tau, neurotransmitter receptors, neuroinflammation, multi-target studies, repurposing pharmacological agents, non-pharmacological interventions, and clinical therapy development for the neuropsychiatric symptoms of dementia. Current clinical trials are ongoing and no results are available as of yet. With the vast choices of drug targets that have been investigated, this review aims to present some insights into future AD drug design and trials and contribute to our ongoing efforts to find the cure. Review Thu, 27 Jun 2024 00:00:00 GMT DanqingXiao, ChenZhang, Thu, 27 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100648 https://www.explorationpub.com/Journals/en/Article/100649 Depression poses a significant global health burden, yet current therapeutic approaches focusing on monoaminergic neurotransmission often fall short of achieving full remission and managing acute episodes effectively. This article explores novel treatment avenues beyond conventional monoaminergic approaches, focusing on emerging strategies targeting glutamatergic modulation, electrophysiological/magnetic brain stimulation techniques, anti-inflammatory agents, gut-brain axis interventions, gamma-aminobutyric acid (GABA) modulation, and psychedelic-assisted therapy. Through a narrative review of recent literature, this paper elucidates the mechanisms, clinical efficacy, safety profiles, and future directions of these innovative treatments. These insights offer valuable perspectives for advancing depression management and bridging existing therapeutic gaps. Review Tue, 09 Jul 2024 00:00:00 GMT AmitJagtiani, Tue, 09 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100649 https://www.explorationpub.com/Journals/en/Article/100650 Depression is on the rise and medication does not always provide satisfactory relief. This raises the question of a treatment gap that has not yet been (sufficiently) addressed. Inflammation and oxidative stress play an important pathophysiological role, which also leads to a deficiency of antioxidants such as vitamin C. This perspective mini-review reflects the results of a PubMed search combining the search terms depression with inflammation, oxidative stress and vitamin C. Vitamin C is an important antioxidant and co-factor for many neuronal metabolic and epigenetic pathways, and a deficiency is associated with depression and cognitive disorders. Inadequate vitamin C blood levels that do not yet result in somatic symptoms may induce neuropsychiatric scurvy, which is associated with increased neuroinflammation and characterized by depression and cognitive impairment. Experimental studies show that vitamin C has multifactorial effects on metabolic pathways relevant to depression. Treatment of vitamin C deficiency, which is more common than appreciated, should be considered in the management of depressed patients. Further studies should investigate whether the pharmacological administration of vitamin C has additional effects beyond the correction of deficiency. Perspective Wed, 10 Jul 2024 00:00:00 GMT ClaudiaVollbracht, MarcWerner, Wed, 10 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100650 https://www.explorationpub.com/Journals/en/Article/100651 A short overview of the main features of progressive myoclonus epilepsies (PMEs), such as Lafora disease (LD), neuronal ceroid lipofuscinoses (NCLs), and myoclonus epilepsy with ragged-red fibers (MERRF) is given. The stress of this review paper is put on one of the PME’s, the Unverricht-Lundborg disease (ULD)—EPM1, which is caused by mutations in the human cystatin B gene (stefin B is an alternative protein’s name). However, different other genes/proteins were found mutated in patients presenting with EPM1-like symptoms. By understanding their function and pathophysiological roles, further insights into the underlying processes of EPM1 can be obtained. On a broader scale, common pathophysiological mechanisms exist between ULD, LD and NCLs, such as, reactive glia, synaptic remodeling, neuronal hyperexcitability, impairements in the lysosomal/endocytosis system, cytoskeletal functions, and mitochondria. Oxidative stress is also in common. By understanding the underlying molecular and cellular processes, early interventions, better therapies and eventually, by using modern stem cell, gene editing or replacement methods, a cure can be expected. Review Thu, 18 Jul 2024 00:00:00 GMT EvaŽerovnik, Thu, 18 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100651 https://www.explorationpub.com/Journals/en/Article/100652 The PRECEDE-PROCEED model is a comprehensive planning and theoretical framework that incorporates epidemiological, environmental, behavioral, and social factors systematically to design, implement, and evaluate health promotion programs. As such, PRECEDE-PROCEED is a highly effective tool for addressing complex and significant public health concerns like postpartum depression (PPD). PPD negatively impacts mothers and their infants, with studies showing that approximately one in eight mothers experience PPD, leading to adverse effects on maternal functioning and infant development. However, access to specialized evidence-based treatment remains significantly limited due to barriers including social determinants of health. This paper explores the application of the PRECEDE-PROCEED model as a planning and theoretical framework for the design and development of MommaConnect, an innovative digital healthcare platform aimed at reducing PPD symptoms and improving maternal-infant interaction while overcoming barriers to treatment. Key components of the MommaConnect design and development process are mapped onto the steps of the PRECEDE-PROCEED model. MommaConnect features are aligned with specific stages of the model, from assessing, predisposing, enabling, and reinforcing factors to designing, implementing, and evaluating the intervention. By leveraging this model, MommaConnect represents a promising innovative approach to address PPD to improve maternal functioning and infant health in a digitally-enabled era. This paper underscores the importance of utilizing a framework like the PRECEDE-PROCEED model in the design and development of innovative healthcare solutions. Protocol Tue, 06 Aug 2024 00:00:00 GMT BobbiePosmontier, June AndrewsHorowitz, Pamela A.Geller, MonaElgohail, MaryMcDonough, KaylaAlvares, JaleesaSmoot, KatieChang, TonyMa, Tue, 06 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100652 https://www.explorationpub.com/Journals/en/Article/100653 There is a complex relationship between circadian rhythm dysfunctions and various psychiatric disorders. Circadian (~24 h) rhythms indicate the rhythmic change of different physiological activities in relation to the environmental light-dark cycle. Shift work, light exposure at night, and chronic and acute jet lag affect circadian rhythm that have a negative impact on psychological functions, and behaviors. Additionally, professional stress, mental instability, and social disintegration influence psychiatric disorders. PubMed/MEDLINE, Springer Nature, Science Direct (Elsevier), Wiley Online, ResearchGate, and Google Scholar databases were searched to collect relevant articles. Circadian rhythm disruption causes impaired neurotransmitter release, impaired melatonin and cortisol rhythm, metabolic dysfunctions, neuroinflammation, and neural apoptosis; collectively these factors influence the development of psychiatric disorders. Circadian dysfunction also alters the expression of several clock control genes in the mesolimbic areas that are associated with pathologies of psychiatric disorders. Additionally, chronotherapy and applications of anti-psychotic medicine can improve psychiatric diseases. This review focuses on the effects of circadian clock dysfunction on the vulnerability of psychiatric disorders and the implications of chronotherapy. Review Fri, 23 Aug 2024 00:00:00 GMT SaptadipSamanta, DebasisBagchi, Fri, 23 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100653 https://www.explorationpub.com/Journals/en/Article/100654 Aim: In people with epilepsy (PWE), relationships and support are critical. From receiving affection to getting help with household and medical activities, support can increase Quality of Life (QoL) and resilience. This article aims to identify how key sources of support are affected by epilepsy over a 9-year period. Methods: This longitudinal study is based on a panel of 51 of the same people measured at three points spread over 9 years—Waves 2, 4, and 5 (2010, 2016/7, and 2019/20). The article reports on supportive relationships affected by epilepsy and four different types of support. It investigates the nature and extent of the effects of epilepsy on support for PWE and how these changed over 9 years. The study uses mixed methods. Results: Measured at Wave 5, affectionate support was the most common, while positive social interaction (PSI) was the least. The study showed that over time, epilepsy was having differential effects on supportive relationships (partnerships and with family and friends). Quantitative results suggest that PWE were coping better over time with the effects of epilepsy on family and friendships. The qualitative analysis showed that in Wave 2 where PWE reported on stigma experienced, it was mainly emotional/informational support, together with some PSI that was evident. In Waves 4 and 5, support including from clinicians and epilepsy associations was presented. Some PWE reported that they wanted emotional/informational support from psychologists/counsellors. Conclusions: Support from partners changed little due to epilepsy over the 9 years, while the effect of epilepsy on support from family and friends diminished over that time. In order to more fully understand the support needs of PWE, a good grasp of the sources of social support, whether from health professionals, partners, wider family, or friends is required. Original Article Thu, 29 Aug 2024 00:00:00 GMT ChristineWalker, Chris L.Peterson, Thu, 29 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100654 https://www.explorationpub.com/Journals/en/Article/100655 Aim: Neuroinflammation is a characteristic of multiple sclerosis (MS). Resveratrol (RSV) has potent antioxidant properties and has emerged as a promising therapeutic agent for various inflammatory diseases. This study investigated the effects of RSV on inflammatory responses via reactive oxygen species (ROS) production and leukocyte cytokine secretion in patients with MS and healthy controls. Methods: The effects of RSV on ROS production in resting and stimulated granulocytes (in the presence of opsonized particles) were assessed using luminol-dependent chemiluminescence. The cytokines interleukin (IL)-10, IL-1β, IL-6, and high mobility group box 1 (HMGB1) in the supernatant of peripheral blood mononuclear cells (PBMNCs) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: RSV significantly downregulated ROS production in resting and stimulated granulocytes in patients with MS and healthy controls. In the control group, RSV reduced IL-6 levels by 49% in the PBMNC supernatant, whereas IL-6 levels remained unchanged in the MS group. Interestingly, higher levels of IL-10 were detected in PBMNC supernatants from patients with MS than in controls. No significant changes were observed in IL-1β and HMGB1 levels in the PBMNC supernatant. Conclusions: Controlling ROS production is a key target for treating inflammatory diseases. Our findings suggest that RSV can effectively modulate ROS production in MS, highlighting its potential as a promising adjunct therapy for controlling oxidative innate immune responses in MS. Original Article Tue, 03 Sep 2024 00:00:00 GMT Pedro HenriqueVillar-Delfino, Regiane PenaforteSantos, Paulo PereiraChristo, José AugustoNogueira-Machado, Caroline Maria OliveiraVolpe, Tue, 03 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100655 https://www.explorationpub.com/Journals/en/Article/100656 Cognitive impairment is a common age-related comorbidity with blood-brain barrier (BBB) leakage a key event. BBB leakage increases with age, but the mechanisms are still not completely understood. In the current article, we briefly discussed the role of neutrophil extracellular traps (NETs) in age-associated increase in cognitive impairment. NETosis is a process neutrophils release web-like structures called NETs composed of DNA, histones, and antimicrobial proteins. These NETs act as physical barriers to trap and kill pathogens, such as bacteria, viruses, and fungi. Excessive NETs formation has been associated with various pathological conditions such as thrombosis, cancer metastasis, inflammatory diseases, and autoimmune disorders. Recent studies further indicated that NETosis plays a key role in the BBB leakage during stroke and depletion of neutrophils can attenuate the pathology of Alzheimer’s disease (AD) in murine models. In the current article, we briefly discussed the putative role of NETosis in BBB leakage and age-related cognitive impairment. It should briefly summarize the main content of the article, and it may include the background, purpose, significance, methods and conclusions of the article. Mini Review Tue, 03 Sep 2024 00:00:00 GMT DivyaSharma, RahulKumar, Tue, 03 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100656 https://www.explorationpub.com/Journals/en/Article/100657 As an integral part of human chronobiology, the circadian system plays a crucial role in regulating key biological functions, including sleep and the intricate hormonal rhythms of melatonin (MLT) and cortisol (CORT). Scholars have increasingly recognized environmental stressors as significant contributors to disturbed sleep patterns. Albeit vigorously discussed individually, the literature lacks comprehensive insights into the synergistic effect of artificial light at night (ALAN) and noise. The aim of this review is to look into the intricate interplay of the ALAN effects on sleep architecture, the modulation of circadian function, and how this influences homeostatic sleep. Furthermore, ALAN suppresses MLT secretion, which is most pronounced in response to short wavelengths of light. In addition, this review will demonstrate how exposure to noise during sleep elevates CORT and noradrenaline levels, which contributes to stress-related diseases and sleep disturbances. ALAN and noise, persistently emitted into the environment, share intrinsic mechanisms with comparable characteristics. Therefore, understanding their combined impact has become increasingly urgent. Pre-sleep exposure to both ALAN and noise acts as a potent stressor, with the potential to disrupt sleep patterns. Interestingly, during sleep, noise emerges as the predominant influence on sleep quality. Moreover, these stressors often synergize and amplify one another’s adverse effects. Thus, limiting their exposure is crucial for cultivating a sustainable environment conducive to quality sleep and overall well-being. Review Fri, 13 Sep 2024 00:00:00 GMT Nahum M.Gabinet, Fri, 13 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100657 https://www.explorationpub.com/Journals/en/Article/100658 Chronic neuropathic pain is a significant public health issue affecting an estimated 1.5 billion individuals worldwide. The mechanisms underlying chronic pain are multifaceted and not fully understood. Chronic pain amplifies specific neural pathways through peripheral and central sensitization triggered by repeated exposure to noxious stimuli, ultimately resulting in physical and emotional pain. Traditional treatment options targeting these mechanisms, such as opioid and non-opioid analgesics, are associated with adverse effects, addiction, and suboptimal pain relief. Using psychedelics to treat chronic pain is an area of growing interest. While psychedelic substances, such as psilocybin, lysergic acid diethylamide, mescaline, and 3,4-methylenedioxymethamphetamine are primarily associated with recreational use or spiritual practices, emerging evidence suggests their potential therapeutic benefits for various mental health disorders, including chronic pain. Psychedelics alter pain perception by directly activating serotonin receptors, exerting anti-inflammatory effects, enhancing descending inhibition, opening a window of neuroplasticity, and facilitating synaptic remodeling. This review mainly elucidates the ongoing research regarding the psychedelic mechanisms of action, pharmacology, clinical applications, and therapeutic potential in treating neuropathic pain. Review Tue, 24 Sep 2024 00:00:00 GMT BushraYasin, ShivaniMehta, GeorgeTewfik, AlexBekker, Tue, 24 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100658 https://www.explorationpub.com/Journals/en/Article/100659 The overt expression of circadian rhythms is a manifestation of the suprachiasmatic nucleus (SCN). This integrated complex function based on the transcriptional/translational feedback loops (TFFLs), neurotransmitters, genes, networking, and synchronization is essential for this molecular mechanism to operate effectively. Neurotransmitters by participating in the entrainment to the environmental light conditions and synchronization contribute to the robustness of the rhythm. Neurotransmitter signaling is the hallmark of circadian rhythm expression. Even during development, neuropeptides contribute to the dramatic cellular, genetic, and network circuit changes. Participating neurotransmitters are seen in afferent inputs, efferent output, and the SCN. There are numerous neurotransmitters involved in SCN function. Astrocytes co-exist with neurons in the SCN. Autonomous clocks seen in astrocytes can drive circadian behavior like neurons. Astrocytes and neurons are acting as two arms of the clock. Coupling through glutamate released from astrocytes gives additional evidence for the role of astrocytes. Glutaminergic signaling from astrocytes may also be responsible for timekeeping. The neurotransmitters can independently and in combination execute the functions making SCN a unique pacemaker for the overt expression of circadian rhythms. This reassessment also highlights its role in underlying molecular mechanisms, genetic linkage, and the recently known role of astrocytes. Review Tue, 24 Sep 2024 00:00:00 GMT VallathReghunandanan, Tue, 24 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100659 https://www.explorationpub.com/Journals/en/Article/100660 Epilepsy, a neurological disorder characterized by recurrent seizures, presents a complex interplay of cellular and molecular mechanisms. The symptoms manifest themselves at various scales, from ion channels to brain regions to behavior in humans. Various screening, treatment, and preventive measures use this knowledge to tackle the disorder effectively. This article aims to summarize the current state of the art in epileptic markers from ion channels, astrocytes, and synaptic imbalance to whole brain Network Dynamics. Recent research has shed light on the critical involvement of astrocytes, the multifunctional glial cells, in the pathogenesis and modulation of epileptic seizures in humans. Astrocytes, once considered as mere supportive cells, are now recognized as active participants in the regulation of neuronal excitability, synaptic transmission, and brain homeostasis. Ion channel imbalance is one of the widely studied areas in the context of epilepsy and is partially addressed in the abstract. Recent advances in computational neuroscience have led to the development of whole brain network models, providing valuable tools for studying the complex dynamics of epileptic seizures. These models integrate diverse biological factors, including neuronal connectivity, synaptic dynamics, and cellular properties, to simulate the spatiotemporal patterns of epileptic activity across brain regions. Through computational simulations and analysis, whole brain network models offer insights into seizure initiation, propagation, and termination mechanisms, shedding light on the dynamic interactions between epileptic foci and distributed brain networks. Moreover, these models facilitate the exploration of network-based biomarkers for seizure prediction and intervention optimization. Challenges and limitations, such as model complexity and validation against experimental data, are also discussed. Despite these challenges, whole brain network models represent a promising approach for advancing our understanding of epilepsy and identifying novel therapeutic strategies. Future research efforts should focus on refining model fidelity, incorporating multimodal data, and translating computational findings into clinically relevant applications, ultimately improving the management and treatment of epilepsy patients. Review Sun, 29 Sep 2024 00:00:00 GMT SwatiBanerjee, ViktorJirsa, Sun, 29 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100660 https://www.explorationpub.com/Journals/en/Article/100661 Aim: Diabetic polyneuropathy is the most described complication in patients with diabetes mellitus. A significant percentage of these patients experience disabling neuropathic pain (painful diabetic polyneuropathy). Small nerve fibers are primarily responsible for peripheral nociception, but objectively assessing its function is challenging. The primary objective of this study was to explore the task execution and outcomes of intra-epidermal electrical stimulation technique that combines nociceptive detection thresholds (NDT) and evoked potentials (EPs) in patients with diabetes. We compared the results of diabetic patients, both with and without painful diabetic polyneuropathy, with those of healthy controls to explore potential clinically relevant information. Methods: The NDT-EP method was applied to 38 patients with diabetes (18 with and 20 without chronic painful neuropathy) and 38 age- and sex-matched healthy controls. Individual mean NDTs, psychometric slopes, EP amplitudes, and the effect of the stimuli on EP amplitudes were analyzed and compared between groups using linear regression. Results: The findings revealed significantly lower detection rates, higher NDTs, and lower psychometric slopes in patients with painful diabetic polyneuropathy than in healthy controls. Both patient groups significantly exhibited lower mean EP amplitudes than healthy controls, which were not linked to pulse amplitudes but influenced by stimulus detection. Conclusions: This study showed altered NDT-EP outcomes in patients with painful diabetic polyneuropathy. Whereas the task execution, NDTs, and psychometric slopes may provide valuable insights into small fiber dysfunction, pulse amplitudes seemed not differently encoded in neurophysiological responses to intra-epidermal electrical stimulation near the detection threshold compared to controls. Future studies should investigate whether the altered NDT-EP outcomes could quantify small fiber dysfunction in patients with diabetes mellitus. We recommend further exploration of NDT-EP measures in other patient groups with nociceptive dysfunction. Original Article Tue, 15 Oct 2024 00:00:00 GMT TomBerfelo, Imre P.Krabbenbos, Boudewijnvan den Berg, Silvano R.Gefferie, Jan R.Buitenweg, Tue, 15 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100661 https://www.explorationpub.com/Journals/en/Article/100662 Aim: Seizure and epilepsy adverse events (AEs) can occur following vaccination. For epilepsy AEs, they are generally expected to only occur at background population frequencies without associations with immunizations. The Vaccine AEs Reporting System (VAERS) collects a subset of AEs experienced by vaccinees, including multiple epilepsy related AEs. This study examines the possibility of immunization associated epilepsy AEs in VAERS occurring above background rates. Methods: Herein, VAERS is retrospectively examined for epilepsy and seizure AEs following immunizations (AEFIs). Reported AEFIs are normalized by total AEFIs for each vaccine. VAERS data is examined by vaccine type, vaccine source, vaccinee gender, and age-stratified for infants. Results: Association signals for examined epilepsy and seizure AEFIs are identified for multiple vaccines when compared to other vaccines with normalized frequencies above expected population background frequencies. Normalized epilepsy AEFI frequencies for children less than 1 year are higher than children aged 1 year for several vaccines. For pairs of matched vaccines from different manufacturers, statistically different epilepsy AEFI normalized frequencies were observed. These matched pairs for multiple vaccines implicate likely vaccine contaminations (e.g., endotoxins) as likely candidates for causing elevated epilepsy and seizure AEFIs. Conclusions: Based on the reported results, delaying some immunizations of a small set of vaccines until children are 1 year of age is predicted to reduce epilepsy AEFI occurrences for these vaccines. For several vaccines, statistically significant differences in epilepsy AEFI normalized frequencies were detected for the same (or similar) vaccine from different manufacturers; this suggests that possible manufacturing contaminant(s) (e.g., endotoxins) as the likely causative agent(s) for observed epilepsy AEFIs above background rates. Eliminating or reducing these possible contaminants is predicted to reduce the observed associations closer to background population levels observed for other vaccines with very low epilepsy AEFI normalized frequencies. Original Article Wed, 16 Oct 2024 00:00:00 GMT Darrell O.Ricke, Wed, 16 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100662 https://www.explorationpub.com/Journals/en/Article/100663 Glioblastoma multiforme (GBM) is the most common malignant primary central nervous system (CNS) tumor. It presents an aggressive pattern, with a tendency for intracranial progression despite optimal treatment. On the other hand, metastases and manifestations outside the CNS are exceptional, and very few cases have been described. The authors submitted a case of a 48-year-old male diagnosed with a left parietooccipital GBM isocitrate dehydrogenase (IDH) wild-type, non-methylated O6-methylguanine-DNA methyltransferase (MGMT). Six months after surgical treatment, followed by a chemotherapy (CT) and radiotherapy scheme, he developed a few subcutaneous erythematous nodules within the surgical scar. A punch biopsy confirmed the histopathology of GBM. The CT scan showed concomitant intracranial progression. We ruled out systemic metastases. As the performance status was good [Karnofsky Performance Status 90 (KPS 90)] and the subcutaneous implants were growing rapidly, limiting the quality of life, we decided to perform palliative surgery to remove the implants. The result was good. Unfortunately, the patient worsened during the following week, after ruling out medical complications, we attributed the worsening to cerebral tumor swelling, revealed in the CT scan, as unresponsive to steroids. He passed away a few days later. Based on the analysis of our case, we intend to provide useful information for the approach to this peculiar manifestation of GBM. Case Report Wed, 16 Oct 2024 00:00:00 GMT MariaCiscar-Fabuel, AlexandreDe Vilalta-Bufurull, GemmaBlanch-Pujol, MarinaRomero-Quintela, GerardPlans-Ahicart, AndreuGabarros-Canals, Wed, 16 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100663 https://www.explorationpub.com/Journals/en/Article/100664 Aim: Patients with tuberous sclerosis complex (TSC) which is caused by hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) often show giant cells in the brain. These giant cells are thought to be involved in epileptogenesis, but the underlying mechanisms are unknown. In this study, we focused on mTORC1 activation and γ-amino butyric acid (GABA)ergic signaling in somatostatin-expressing inhibitory neurons (SST-INs) using TSC-related epilepsy model mice. Methods: We analyzed the 8-week-old Tsc2 conditional knockout (Tsc2 cKO) mice, which have epileptic seizures that are cured by sirolimus, an mTORC1 inhibitor. After the occurrence of epileptic seizures was confirmed, Tsc2 cKO mice were treated with vehicle or sirolimus. Then, their brains were investigated by hematoxylin and eosin staining, immunohistochemical staining and immunoblotting assay. Results: As in TSC patients, giant cells with hyperactivation of mTORC1 were found in the cerebral cortex of Tsc2 cKO mice. These giant cells were mainly SST-INs in the cortical layers 4/5. Giant cells showed decreased expression of GABA type A receptor subunit α1 (GABAAR-α1) compared with normal size cells in control mice and Tsc2 cKO mice. In addition, decreased GABAAR-α1 expression was also confirmed by immunoblotting assay of the whole cerebral cortex. In the cerebral cortex of sirolimus-treated Tsc2 cKO mice, whose epileptic seizures were cured, decreased GABAAR-α1 expression was recovered to the same level as in control mice. Conclusions: These results suggest that the epileptic seizures in Tsc2 cKO mice are caused by the deregulation of GABAergic signaling through mTORC1 activation of SST-INs localized in cortical layers 4/5. Original Article Wed, 30 Oct 2024 00:00:00 GMT FumikiYamashita, MakikoKoike-Kumagai, ManabuFujimoto, MariWataya-Kaneda, Wed, 30 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100664 https://www.explorationpub.com/Journals/en/Article/100665 Glioblastoma multiforme (GBM) is characterized by its infiltrative growth pattern and high recurrence rate despite treatment. While local progression within the central nervous system (CNS) is the rule, manifestations outside the CNS, particularly skin and subcutaneous metastases, are very infrequent and seldom reported in the literature. The authors reviewed the current understanding of this rare condition, with the main purpose of giving visibility to its clinical presentation and prognostic implications, thus improving clinical management and encouraging research in this area. A PubMed, Cochrane Library, and EMBASE search from database inception through March 2024 was conducted. In this way, we compiled a total of thirty-five cases in our review. As far as we know, our work gathers the largest number of patients with this condition. Remarkably, we observed that the typical presentation of soft-tissue high-grade glioma metastases is the finding of subcutaneous erythematous nodules in patients previously operated on for a primary CNS tumor, within the craniotomy site and nearby, mostly in the first year after the initial surgery. It was also noted that there is a trend of developing a concomitant CNS recurrence and/or other metastases in different locations, either simultaneously or subsequently. From here, we propose some possible mechanisms that explain the extracranial spread of GBM. We concluded that a poor outcome is expected from the diagnosis of skin and subcutaneous metastases: the mean overall survival was 4.38 months. Yet, assessing individual characteristics is always mandatory; a palliative approach seems to be the best option for the majority of cases. Review Wed, 30 Oct 2024 00:00:00 GMT MariaCiscar-Fabuel, AlexandreDe Vilalta-Bufurull, GemmaBlanch-Pujol, MarinaRomero-Quintela, GerardPlans-Ahicart, AndreuGabarros-Canals, Wed, 30 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100665 https://www.explorationpub.com/Journals/en/Article/100666 Melatonin is widely available as a dietary supplement and/or medicine for sleep. It is an endogenous hormone produced in the pineal gland of the brain, with metabolites providing additional beneficial mechanisms such as supporting long-term memory. Melatonin is well known as a hormone that plays a role in the circadian rhythm (sleep cycle), but additional mechanisms such as antioxidant, and anti-inflammatory activity are elucidated from animal research models. This article discusses melatonin supplementation and the current understanding of how it may provide benefits beyond the use as a sleep aid including a review of the evidence in how it may aid in mitigating components of cognitive decline. Perspective Tue, 26 Nov 2024 00:00:00 GMT Leticia A.Shea, Tue, 26 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100666 https://www.explorationpub.com/Journals/en/Article/100667 Aim: We aimed to undertake a small study comparing buccal midazolam and rectal diazepam in the emergency out-of-hospital treatment of prolonged or serial epileptic seizures in children. We wanted to see if the parent/carer could not only administer the emergency medication but also document the timings and outcomes of the trial. We also aimed to demonstrate parental preference for either treatment. Methods: This was an open-label, randomised, cross-over clinical trial. The primary outcome was parental preference, secondary outcomes included therapeutic success (seizure stopped within 10 minutes of treatment with no relapse in the next 24 hours), and adverse events. Research Ethics Committee approval and appropriate written informed consent were obtained for all participants. Identical convenient age-related doses of buccal midazolam and rectal diazepam were used: for those aged 6 to < 12 months, 2.5 mg was prescribed; for those aged 1 to < 5 years, 5 mg; 5 to < 10 years, 7.5 mg; 10 years and over, 10 mg. Appropriate randomisation and statistical methods were used. Results: Twelve children, three males, aged 2.5–8 (median 5) years, including 10/12 with developmental delay or intellectual impairment completed the trial. Each participant had between 2–4 types of epileptic seizure, was taking 2–3 different regular antiseizure medications, and had been previously on 2–9 (median 3) regular other antiseizure medications in the past. Nine of twelve parents preferred buccal midazolam, 1/12 preferred rectal diazepam (P < 0.05). Therapeutic success was seen in 7/12 participants with either treatment. No respiratory depression was seen in this small trial. Conclusions: Buccal midazolam was clearly preferred to rectal diazepam by parents. This small study was not powered to show a difference in efficacy and adverse effects. The study did show that the cross-over design with parents recording trial data, including data for the outcome measures was feasible. Original Article Fri, 20 Dec 2024 00:00:00 GMT Hoong WeiGan, EvangelineWassmer, William P.Whitehouse, Fri, 20 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100667 https://www.explorationpub.com/Journals/en/Article/100669 Aim: Mitochondria are essential for brain development, and the presence of different mitochondrial types is called mitochondrial heteroplasmy. Mitochondrial dysfunction is a central aspect of many people’s neurological diseases. Heteroplasmy is commonly observed in eukaryotes due to mitochondrial genome (mtDNA) mutation, paternal leakage, mitochondria transplantation/mitotherapy, and somatic cell nuclear transfer (SCNT). In this study, we developed two novel approaches to construct mitochondrial heteroplasmy cellular models. Methods: Model 1: the yak cell line (Bos grunniens) was transfected with p-eGFP-neo plasmid while mammary alveolar cell-T (MAC-T) cell line from cattle cells (Bos taurus) was stained with MitoTracker Deep Red FM. The yak cell line was used as recipient cells which fused with enucleated cattle cells. Model 2: The cattle cell line was stained with MitoTracker Green FM while yak cells were stained with MitoTracker Deep Red FM. Cattle cells were used as recipient cells which fused with enucleated yak cells. Following fusions, the single cells exhibiting dual positive fluorescence signals were sorted into 96-well plate by fluorescence-activated cell sorting. Confocal fluorescence examination confirmed that the cells with mitochondrial heteroplasmy were sorted. Results: The two methods can generate a variety of mitochondrial heteroplasmy cells of interest which can aid in understanding the patterns and influencing factors underlying heteroplasmy changes. Conclusions: The mitochondrial heteroplasmy cellular model contributes to managing heteroplasmy mitochondrial changes and preventing the development of mitochondrial declines. Original Article Tue, 14 Jan 2025 00:00:00 GMT YaningHu, LinJiang, WenLiu, XingboZhao, Tue, 14 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100669 https://www.explorationpub.com/Journals/en/Article/100671 Intracranial artery dolichoectasia (IADE) is a vascular anomaly characterized by dilation and/or tortuosity of one or more intracranial arteries. While many cases are incidental findings on imaging, the associated ischemic neurological complications of IADE can be severe and must be promptly recognized. This study aims to increase awareness among general practitioners and neurologists regarding this rare and potentially life-threatening condition. We utilized reputable databases for this scoping review, including PubMed, Scopus, and Google Scholar, from database inception through September 2024, using a combination of terms such as “Dolichoectasia of Basilar Artery”, “Intracranial Dolichoectasia”, and “Ischemic Stroke”. Our scoping review revealed that IADE is a challenging and often underdiagnosed condition, with an estimated prevalence of less than 1% in the general population. Hypertension, atherosclerosis, and advanced age are well-documented risk factors. To minimize the risk of misdiagnosis, we briefly elucidated the pathophysiology of IADE, correlating it with clinical and radiological features. We discuss the diagnostic criteria for IADE based on radiological imaging, addressing the advantages and limitations of different techniques. Finally, we highlight the unmet clinical needs related to IADE management, which may involve pharmacological and surgical therapies tailored to individual cases, with careful consideration of safety and efficacy. Review Sun, 26 Jan 2025 00:00:00 GMT Lorena DellagnesiDepieri, Renan Rodrigues Neves Ribeirodo Nascimento, Lorena SouzaViana, Sun, 26 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100671 https://www.explorationpub.com/Journals/en/Article/100668 Depression is characterized by affective symptoms and neuropsychological deficits. After treatment, affective symptoms frequently remit, but cognitive alterations may remain affecting the lives of people and having an impact on health, economy, and societies. The present work describes the methods, procedures, and equipment for a randomized three-arm controlled experiment designed to measure the effects of exergames on executive functions (EFs) under depression. EFs are complex cognitive functions that are essential for organizing information, planning an action, reasoning, decision-making, and problem-solving. Literature shows that EFs are compromised in depression, affecting daily-life activities and other cognitive domains. To conduct the experiment, depressed middle-aged adults will be randomly distributed into three experimental groups: an intervention group training with exergames, an active control group training only with cognitive video games, and a passive control group or wait-list. EFs are evaluated at three different time points: pre-post intervention, and three months follow-up, using the Wisconsin Card Sorting Test (WCST). Researchers will collect cognitive-behavioral and neural information [event-related potentials (ERPs)]. Results will be explored by performing analysis of variance to compare the outcomes of the diverse groups at the three different time points, understanding the benefits of exergames in terms of EFs under depression. The study of simultaneous multidomain interventions in depression holds promise for the development of novel approaches, to implementing psychological and neuropsychological health [this experiment is part of a registered clinical trial entitled “MUDgame” (ClinicalTrials.gov identifier NCT06536530). Registered on August 2024, https://clinicaltrials.gov/study/NCT06536530]. Protocol Mon, 23 Dec 2024 00:00:00 GMT EloisaRuiz-Marquez, Mon, 23 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100668 https://www.explorationpub.com/Journals/en/Article/100670 Epilepsy, a complex and widespread neurological disorder, has evolved in its understanding from ancient misconceptions to modern scientific advancements. This special issue highlights pivotal research and reviews on the mechanisms underlying epilepsy, innovative treatment strategies, and the psychosocial dimensions of living with this condition. Together, these contributions reflect the growing interdisciplinarity and depth in epilepsy research. Editorial Wed, 15 Jan 2025 00:00:00 GMT JinweiZhang, Wed, 15 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100670 https://www.explorationpub.com/Journals/en/Article/100672 Intracellular amyloid β oligomers (AβOs) have been linked to Alzheimer’s disease (AD) pathogenesis and to the neuronal damage in this neurodegenerative disease. Calmodulin, which binds AβO with very high affinity, plays a pivotal role in Aβ-induced neurotoxicity and has been used as a model template protein for the design of AβO-antagonist peptides. The hydrophobic amino acid residues of the COOH-terminus domain of Aβ play a leading role in its interaction with the intracellular proteins that bind AβO with high affinity. This review focuses on Aβ-antagonist hydrophobic peptides that bind to the COOH-terminus of Aβ and their endogenous production in the brain, highlighting the role of the proteasome as a major source of this type of peptides. It is emphasized that the level of these hydrophobic endogenous neuropeptides undergoes significant changes in the brain of AD patients relative to age-matched healthy individuals. It is concluded that these neuropeptides may become helpful biomarkers for the evaluation of the risk of the onset of sporadic AD and/or for the prognosis of AD. In addition, Aβ-antagonist hydrophobic peptides that bind to the COOH-terminus of Aβ seem a priori good candidates for the development of novel AD therapies, which could be used in combination with other drug-based therapies. Future perspectives and limitations for their use in the clinical management of AD are briefly discussed. Review Tue, 25 Feb 2025 00:00:00 GMT CarlosGutierrez-Merino, Tue, 25 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100672 https://www.explorationpub.com/Journals/en/Article/100675 Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. It presents a significant challenge in terms of accurate diagnosis, disease progression monitoring, and the development of effective treatments. This article addresses the role of neuroimaging as an advancing tool for diagnosis, monitoring progression, and treatment of AD. A comprehensive review of existing literature on the use of neuroimaging in AD was conducted using various databases. The different imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), were examined in terms of their ability to detect amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), the hallmark pathological features of AD. Neuroimaging enables the visualization of Alzheimer-related biomarkers, such as Aβ plaques, tau protein tangles, neuro-inflammation, and synaptic dysfunction, providing valuable insights into disease pathophysiology and progression. These imaging techniques assist in the early detection of AD, distinguishing it from other conditions and evaluating the effectiveness of treatments. This has the potential to significantly transform the way AD is managed clinically. By providing insights into the molecular changes that occur in the brain during the course of the disease, neuroimaging can facilitate early diagnosis, monitor disease progression, and inform treatment decisions. Furthermore, neuroimaging holds great potential for accelerating drug development by allowing researchers to assess the efficacy of novel therapies in real time. Overall, the integration of neuroimaging into the clinical management of AD has the potential to revolutionize the way we approach diagnosis, treatment, and research in AD. Review Wed, 26 Feb 2025 00:00:00 GMT JuliusMulumba, RuiDuan, BoLuo, JiangWu, MuhammadSulaiman, FengWang, YongYang, Wed, 26 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100675 https://www.explorationpub.com/Journals/en/Article/100674 The use of neurostimulation devices for the treatment of Alzheimer’s disease (AD) is a growing field. In this review, we examine the mechanism of action and therapeutic indications of these neurostimulation devices in the AD process. Rapid advancements in neurostimulation technologies are providing non-pharmacological relief to patients affected by AD pathology. Neurostimulation therapies include electrical stimulation that targets the circuitry-level connection in important brain areas such as the hippocampus to induce therapeutic neuromodulation of dysfunctional neural circuitry and electromagnetic field (EMF) stimulation that targets anti-amyloid molecular pathways to promote the degradation of beta-amyloid (Aβ). These devices target specific or diffuse cortical and subcortical brain areas to modulate neuronal activity at the electrophysiological or molecular pathway level, providing therapeutic effects for AD. This review attempts to determine the most effective and safe neurostimulation device for AD and provides an overview of potential and current clinical indications. Several EMF devices have shown a beneficial or harmful effect in cell cultures and animal models but not in AD human studies. These contradictory results may be related to the stimulation parameters of these devices, such as frequency, penetration depth, power deposition measured by specific absorption rate, time of exposure, type of cell, and tissue dielectric properties. Based on this, determining the optimal stimulation parameters for EMF devices in AD and understanding their mechanism of action is essential to promote their clinical application, our review suggests that repeated EMF stimulation (REMFS) is the most appropriate device for human AD treatments. Before its clinical application, it is necessary to consider the complicated and interconnected genetic and epigenetic effects of REMFS-biological system interaction. This will move forward the urgently needed therapy of EMF in human AD. Review Wed, 26 Feb 2025 00:00:00 GMT Felipe P.Perez, BrettWalker, JorgeMorisaki, HaithamKanakri, MaherRizkalla, Wed, 26 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100674 https://www.explorationpub.com/Journals/en/Article/100676 Purinergic signaling, mediated by ATP and adenosine receptors, plays a crucial role in cellular communication and homeostasis within the central nervous system (CNS), particularly by regulating synaptic activity, glial cell functions, and neuroplasticity. Glial cells, including astrocytes and microglia, contribute to both short-term processes, such as neurotransmission and neuroinflammation, and long-term functions, including synaptic remodeling, tissue repair, and behavioral adaptation. Dysregulation of purinergic signaling in these cells has been implicated in the pathogenesis of various neurodegenerative and neuropsychiatric disorders. This article explores the evolving concept of the synapse, highlighting the active role of glial cells in synaptic modulation and emphasizing the significance of purinergic signaling in synaptic function and responses to conditions such as injury and neurotoxicity. Specifically, it examines the roles of ATP and adenosine receptors—such as P2X4, P2X7, P2Y1, and P2Y12—in mediating key astrocytic and microglial functions, including neuroinflammation, phagocytosis, synaptic plasticity, and neuronal damage. Furthermore, the article discusses the involvement of purinergic receptors in neurological disorders such as epilepsy, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ischemic stroke, Rett syndrome, and autism spectrum disorder, as well as potential therapeutic strategies targeting these receptors to mitigate inflammation, promote tissue repair, and improve clinical outcomes. Review Wed, 12 Mar 2025 00:00:00 GMT Moawiah MNaffaa, Wed, 12 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100676 https://www.explorationpub.com/Journals/en/Article/100677 Aim: Alzheimer’s disease (AD) is associated with several electrophysiological biomarkers. These biomarkers are associated with global decline in cognition and a diagnosis of AD. However, a specific electrophysiological biomarker is not characterized as normal-functioning older adults convert to AD. The longitudinal retrospective study was conducted to describe an electrophysiological biomarker indicator for AD as normal-functioning older adults convert to a diagnosis in the AD continuum over a 2-year period. Methods: The study was conducted with 54 community-residing older adults, ranging from normal functioning to a diagnosis of AD. All initial and follow-up electrophysiological evaluations were completed in the New York University Brain Research Laboratories, and overall decline assessments with the Global Deterioration Scale (GDS) were completed in the New York University Aging and Dementia Research Center. Data included measurements from the GDS and raw resting-state electroencephalogram (rsEEG), which was transformed into quantitative EEG (qEEG) data. Data analysis consisted of descriptive statistics and a Kruskal-Wallis test. The level of significance was 0.05 with a moderate effect size. Topographic brain images displayed electrophysiological biomarkers. Results: A consistently increasing rsEEG theta frequency (P ≤ 0.01) occurred as normal-functioning older adults converted to AD across all GDS stages from the frontal to posterior regions with the progressive global decline. No discernible consistent electrophysiological changes were observed for rsEEG delta, alpha, or beta frequencies over all GDS stages. The GDS stages differed at baseline and follow-up (P ≤ 0.01). The rsEEG theta frequency increased with the progressive global decline across the GDS stages. Conclusions: The consistently increasing rsEEG theta frequency may be an electrophysiological biomarker indicator for AD from normal functioning to a diagnosis within the AD continuum. This biomarker will enhance the assessment of the risk, onset, and progression of AD and potentially inform the treatment of AD. Original Article Mon, 24 Mar 2025 00:00:00 GMT Ezra C.Holston, Mon, 24 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100677 https://www.explorationpub.com/Journals/en/Article/100678 The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on a global scale. One of the main molecular mechanisms responsible for the development of Neuro-PASC, in individuals of all ages, is the formation and inadequate proteolysis/clearance of phase-separated amyloid crystalline aggregates—a hallmark feature of aging-related neurodegenerative disorders. Amyloidogenesis during viral infection and persistence is a natural, inevitable, protective defense response that is exacerbated by SARS-CoV-2. Acting as chemical catalyst, SARS-CoV-2 accelerates hydrophobic collapse and the heterogeneous nucleation of amorphous amyloids into stable β-sheet aggregates. The clearance of amyloid aggregates is most effective during slow wave sleep, when high levels of adenosine triphosphate (ATP)—a biphasic modulator of biomolecular condensates—and melatonin are available to solubilize amyloid aggregates for removal. The dysregulation of mitochondrial dynamics by SARS-CoV-2, in particular fusion and fission homeostasis, impairs the proper formation of distinct mitochondrial subpopulations that can remedy challenges created by the diversion of substrates away from oxidative phosphorylation towards glycolysis to support viral replication and maintenance. The subsequent reduction of ATP and inhibition of melatonin synthesis during slow wave sleep results in incomplete brain clearance of amyloid aggregates, leading to the development of neurological manifestations commonly associated with age-related neurodegenerative disorders. Exogenous melatonin not only prevents mitochondrial dysfunction but also elevates ATP production, effectively augmenting the solubilizing effect of the adenosine moiety to ensure the timely, optimal disaggregation and clearance of pathogenic amyloid aggregates in the prevention and attenuation of Neuro-PASC. Review Tue, 25 Mar 2025 00:00:00 GMT DorisLoh, Russel J.Reiter, Tue, 25 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100678 https://www.explorationpub.com/Journals/en/Article/100679 Not applicable. Editorial Tue, 25 Mar 2025 00:00:00 GMT Dirk M.Hermann, ErtugrulKilic, Tue, 25 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100679 https://www.explorationpub.com/Journals/en/Article/100680 Neuropathic pain (NP) is a significant global health challenge, affecting an estimated 7–10% of the population. Painful diabetic neuropathy (PDN), a severe complication of diabetes, impacts approximately one in every three diabetic patients. With the rising global prevalence of diabetes, PDN is projected to become an increasingly urgent health concern. Current treatments for PDN often provide inadequate pain relief and are associated with adverse side effects, emphasizing the need for safe and effective therapeutic options. This review examines the limitations of existing pharmacological therapies for PDN and presents the sigma-1 receptor (S1R) as a promising therapeutic target. We explore the biological role of S1R, its implication in NP and PDN, its structural biology, and the expanding preclinical and clinical evidence supporting its potential. Furthermore, we present evidence for various S1R antagonists in addressing NP and PDN, with a particular focus on E-52862 and [18F]FTC-146. These compounds represent first-in-class ligands for therapeutic and diagnostic applications, respectively, marking significant advances in the development of S1R antagonists. This review underscores the potential of S1R antagonism as a strategy for developing more effective treatments for PDN, with the ability to significantly improve patient outcomes. Review Tue, 01 Apr 2025 00:00:00 GMT YouyiPeng, QiangZhang, ShanChen, Tue, 01 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100680 https://www.explorationpub.com/Journals/en/Article/100681 Glioma is a highly aggressive brain cancer associated with significant mortality. Despite advances in diagnostic and therapeutic strategies, the prognosis for glioma patients remains poor due to limited diagnostic accuracy and monitoring capabilities. Translocator protein (TSPO) is a mitochondrial protein implicated in various cancers, including glioma, where it plays a significant role in cell survival, proliferation, and chemo-resistance. This review article aimed to comprehensively analyze the role of TSPO in glioma, particularly its potential applications in enhancing diagnostic methods and therapeutic strategies. Molecular imaging techniques have emerged as promising tools for non-invasive diagnosis, disease progression monitoring, and treatment selection of gliomas. A comprehensive literature review was conducted to explore TSPO’s expression patterns, biological functions, and applications in molecular imaging. Studies utilizing positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and other imaging modalities were included. TSPO is overexpressed in glioma cells, particularly in high-grade tumors, correlating with tumor aggressiveness and patient prognosis. TSPO-targeted imaging agents demonstrate high specificity and sensitivity for glioma detection, positioning TSPO as a promising marker for accurate diagnosis and therapeutic monitoring. Future studies should focus on optimizing TSPO imaging protocols, validating their clinical utility, and exploring combined imaging modalities to improve diagnostic precision. Review Wed, 02 Apr 2025 00:00:00 GMT JuliusMulumba, BoLuo, JiangWu, FengWang, YongYang, Wed, 02 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100681 https://www.explorationpub.com/Journals/en/Article/100682 Alzheimer’s disease (AD), the term “dementia”, describes a specific neuropathology together with the development and progression of age-related cognitive and functional loss. Formononetin is naturally occurring isoflavone recognized for its potential health benefits, anti-oxidant, anti-inflammatory, anti-cancer, and anti-apoptotic properties. Neurodegenerative disorders arise from the gradual loss of function and eventual death of nerve cells in the brain or peripheral nervous system. Astragalus membranaceus is a traditional plant with a variety of pharmacological and biochemical properties, including antiviral, anti-hyperglycaemic, and immunomodulatory effects. Moreover, the expression of membrane-bound and soluble receptor for advanced glycation end products (RAGE) is enhanced in the AD brain due to increased levels of soluble and insoluble amyloid-beta (Aβ) peptides. Additionally, in inflammatory circumstances, leukocytes’ firm attachment and transmigration to endothelial cells are regulated by intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Formononetin also possesses anti-bacterial, anti-inflammatory, anti-cancer, anti-oxidant, and estrogenic activity. Formononetin has emerged as a promising agent in the modulation of mediators involved in neurodegenerative disease. Formononetin might modulate nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway to potentiate the anti-Alzheimer’s activity. Additionally, formononetin might inhibit the Aβ/RAGE interaction which further inactivates the activity of extracellular signal regulated kinase (ERK), Janus kinase (JNK) signaling pathway that results in the reduction of nuclear translocation of nuclear factor kappa B (NF-κB) and also reduces the cytokines level to ameliorate AD. It might inhibit the ICAM, VCAM, and THP-1 proteins. Therefore, this compound offers potential therapeutic benefits by reducing cytokine levels to ameliorate AD. This review article is designed to explore the mechanistic interplay underlying the anti-Alzheimer’s effect of A. membranaceus, especially formononetin. Mini Review Wed, 02 Apr 2025 00:00:00 GMT ManpreetKaur, ShivangiSingh, AvikramjeetSingh, AnishSingh, Wed, 02 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100682 https://www.explorationpub.com/Journals/en/Article/100683 “Functional” gut disorders are clinical conditions frequently encountered in clinical practice, often characterized by abnormalities of the intestinal sensory and motor functions. Although traditionally believed not harboring organic abnormalities, some of these disorders have been demonstrated to have more or less subtle involvement of the enteric nervous system. This involvement has been especially documented for enteric glial cells, even though other elements may be involved. Given the pivotal role of enteric glial cells in gut pathophysiology and their evident abnormalities in some disorders of gut-brain interaction, it may be time to reconsider their role and recognize them as an important pathophysiological factor in these conditions. Thus, due to the prominent neuronal and glial involvement in some clinically severe forms, it is proposed that at least some of the “functional” gut disorders should be reclassified as enteric neuro-gliopathies. Perspective Fri, 11 Apr 2025 00:00:00 GMT GabrioBassotti, Fri, 11 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100683 https://www.explorationpub.com/Journals/en/Article/100684 Aim: Cognitive complaints are frequent among cancer patients. These issues can significantly affect the patient’s quality of life and are linked to a higher risk of developing dementia. However, their occurrence does not consistently correlate with measurable objective cognitive dysfunction, which contributes to their negligence in oncological care. Thus, this study aimed to examine the relationship between subjective and objective measures of cognitive function in patients without CNS involvement in a developing context. Methods: A cross-sectional study was conducted with 50 patients aged 18 and above shortly after diagnosis of non-CNS cancer but before any systematic treatment at a tertiary hospital in Gauteng. The patients completed a self-perceived cognitive impairment (PCI) assessment, and the mini-Montreal Cognitive Assessment (mini-MoCA) as an objective measure of cognition. Correlational analyses were conducted to examine the relationship between self-perceived cognitive problems and performance on the mini-MoCA. Results: The results of the study revealed the presence of both self-perceived cognitive problems and objective cognitive impairments among the study cohort. There was a small non-significant association between self-PCI and the objective measure of cognitive impairment on the mini-MoCA, rs(43) = 0.220, P = 0.147. Notably, only the memory sub-domain showed a significant but moderate positive association with self-PCI, rs(43) = 0.325, P = 0.029. Conclusions: This study offers initial evidence of both subjective and objective cognitive impairment in non-CNS cancer patients before treatment in a resource-constrained setting. While there was a small non-significant association between global objective cognitive impairment and patients’ PCIs, a significant moderate association was revealed between the memory sub-domain and PCI. These results underscore the need for thorough cognitive assessment before treatment, as both the presence of cognitive impairment and patients’ perceptions of it can influence treatment compliance and everyday functioning. Original Article Thu, 17 Apr 2025 00:00:00 GMT Antonio G.Lentoor, Tiro B.Motsamai, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100684 https://www.explorationpub.com/Journals/en/Article/100686 Neuropathic pain, defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory system”, has an estimated prevalence of 7–9.2% in the general population and is associated with poorer health-related quality of life than other types of pain. Diagnosis can be improved by the use of diagnostic algorithms, but treatment remains rather unsatisfactory, with only 30–40% of patients achieving an acceptable response. Some authors have suggested that the poor results in the treatment of neuropathic pain may be related to the different mechanisms present in each patient and have tried to correlate them with clinical characteristics in order to evaluate possible targeted treatments. This approach has been used in some studies evaluating the response to specific pharmacotherapies in clusters of patients, with encouraging results but still limited applicability to clinical practice. In this narrative review, we attempt to analyse the literature suggesting possible pathogenetic mechanisms manifested along the nociceptive pathway due to a lesion or disease of the nervous system; aware of the limitations of exploring such a wide field, we look for conditions that could be targeted by the available pharmacological or interventional treatment options. Functional changes may occur in the nociceptive system from the periphery to the cerebral cortex, in particular in the nociceptive terminals, along the first-order neuron and the dorsal root ganglion, at the first synapses, or at supraspinal levels. Clinical assessment is the first step in the study of anatomical and functional changes; the diagnostic hypothesis should be confirmed, if possible, by instrumental studies or diagnostic blocks or procedures to guide an individualised therapeutic algorithm from less to more invasive treatments. Review Sun, 27 Apr 2025 00:00:00 GMT LauraDemartini, CesareBonezzi, Sun, 27 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100686 https://www.explorationpub.com/Journals/en/Article/100685 Aim: This study is to better understand how the transient ion transport activity of touch receptors could change the graded potential to stimulate an action potential firing. Methods: The latest transmembrane-electrostatically localized protons/cations charges (TELC) theory is employed for numerical analysis to calculate the neural touch signal transduction responding time required to fire an action potential spike. Results: A neural action potential spike was constructed successfully using newly developed time-dependent TELC-based neural transmembrane potential integral equations (Equations 5, 6, and 7). The results explicated that the TELC curve has an inverse relationship with neural transmembrane potential since its curve appears as an inverse mirror image to the action potential spike. Based on the TELC density at resting membrane potential of –70 mV calculated to be 3,900 (excess protons + cations) per μm2 and that at the stimulation threshold level (–55 mV) calculated to be 3,100 (excess protons + cations) per μm2 on extracellular membrane surface, the neural touch signal transduction responding time from PIEZO channel ion conduction to reduce the TELC density to the stimulation level of 3,100 TELC per μm2 has now, for the first time, been calculated for action potential firing. Conclusions: The activity of a single or a few PIEZO channels may be sufficient to generate a “graded potential” to trigger an action potential spike firing. With a high number (200–300) of PIEZO channels activated by touch, it can generate the required “graded potential” to reach the stimulation threshold level (–55 mV) within a neural touch signal transduction time as fast as 0.3 ms. The calculated neural touch signal transduction responding time (e.g., 0.3 ms) may have fundamental implications not only for neuroscience but also for other science and technology fields such as bioengineering and sports physiology. Original Article Sun, 27 Apr 2025 00:00:00 GMT James WeifuLee, Sun, 27 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100685 https://www.explorationpub.com/Journals/en/Article/1006100 Congenital hydrocephalus (CH) is an extreme cerebrospinal fluid (CSF) condition that affects brain development. Current medical treatments, such as ventriculoperitoneal shunting and endoscopic third ventriculostomy, are invasive and susceptible to complications. The subventricular zone (SVZ) is involved in CH, but investigations are hindered by conventional models. Here, we introduce SVZonChip, a dynamic 3D microfluidic device simulating SVZ physiology and CSF dynamics, presenting a proof-of-concept system that could be applied for studying CH. This bioengineered device provides a translational bridge between disease modeling and therapeutic discovery, opening up avenues for non-invasive treatments. Perspective Wed, 23 Jul 2025 00:00:00 GMT IoannisAngelopoulos, Wed, 23 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006100 https://www.explorationpub.com/Journals/en/Article/100687 Aim: To report the incidence, characteristics, and prognosis of spontaneous intracerebral hemorrhage (ICH) in North Karelia Central Hospital Primary Stroke Center (PSC). Methods: All patients admitted with ICH to North Karelia Central Hospital between January 1, 2021, and August 8, 2023, were identified from the center’s prospectively updated stroke care database. Post-hospital care data on outcomes were retrospectively updated between May 27 and June 5, 2024. Results: During the entire study period, we identified altogether 56 ICH patients, of whom two thirds were men. The mean annual incidence of 2021–2022 was 12.3/100,000, and in the population 19–49 years of age, 1.8/100,000. Three months after the stroke, 50% of the patients were functionally independent. In-hospital mortality was 5%, and altogether 11 patients (20%) died during the follow-up (mean 1.72 years). In multivariate analyses, diabetes was associated with mortality [hazard ratio: 3.50, 95% confidence interval (CI): 1.02–11.95], and age was associated with functional outcome in three-month follow-up (odds ratio: 1.060, 95% CI: 1.015–1.107). New-onset epilepsy was diagnosed in three patients (6%) during the follow-up (mean: 1.84 years). Conclusions: Short-term functional outcome of ICH was mostly favorable, continuing long-term trends of improving outcomes after stroke. Efficacy of multiple interventions care bundle in the treatment of ICH in a PSC-level hospital, a shift of using direct oral anticoagulants (DOACs) instead of warfarin, and improved health status of elderly citizens could be contributing to the better outcome. Original Article Thu, 08 May 2025 00:00:00 GMT Jussi O.T.Sipilä, JariToivanen, JuhaPääkkönen, LiisuBalk, MohamedHassan, MattiHeikkinen, AlbinaKettunen, AylaMehdiyeva, Anna MaijaSaukkonen, JohannaWillman, Anne-MariKantanen, Thu, 08 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100687 https://www.explorationpub.com/Journals/en/Article/100688 CD36 is a transmembrane protein that plays a role in various biological processes, including oxidized low-density lipoprotein and fatty acid uptake as well as regulatory control for inflammation signaling. Its robust expression in monocytes and macrophages associated with its ability to translocate fatty acids linked this scavenger receptor to foam cell formation and atherosclerosis. In the context of ischemic stroke, CD36 has been shown to contribute to brain injury and inflammation. Preclinical studies have demonstrated that CD36 expression increases in the brain after stroke and that inhibiting CD36 can reduce infarction size and improve neurological outcomes in animal models. These findings suggest that CD36 may be a potential therapeutic target for ischemic stroke. However, no clinical trials addressing CD36 and acute ischemic stroke are registered in the American or European databases. This review will discuss the relationship between CD36 and ischemic stroke and present some clinical findings in patients with single nucleotide polymorphisms of the CD36 gene. Review Mon, 12 May 2025 00:00:00 GMT Ana-MariaDobri-Nicoară, Ionela DanielaPopescu, ElenaCodrici, MariaDudău, Ana-MariaEnciu, CristianaTanase, Mon, 12 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100688 https://www.explorationpub.com/Journals/en/Article/100689 The choroid plexus, pivotal for cerebrospinal fluid (CSF) regulation and blood-CSF barrier function, becomes a focal point for primary central nervous system lymphoma (PCNSL). This article delves into a case of this uncommon presentation, highlighting diagnostic challenges, treatment complexities, and post-treatment outcomes. A 30-year-old Lebanese patient with mild headaches and vomiting was initially diagnosed with vasculitis but later confirmed through endoscopic biopsy to have diffuse large B-cell lymphoma of the choroid plexus. Treatment with intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy led to gradual neurological improvement. Treatment strategies, aligned with PCNSL standards, include intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy, leading to gradual neurological improvement post-treatment. Prognostic factors, such as age and specific brain area involvement, guide tailored treatment plans. This report emphasizes the need for a multidisciplinary approach, increased awareness, and ongoing research for optimal outcomes in PCNSL cases involving the choroid plexus. Case Report Wed, 21 May 2025 00:00:00 GMT AliMsheik, AymanMawassi, ZeinabAl Mokdad, Wed, 21 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100689 https://www.explorationpub.com/Journals/en/Article/100691 Ectonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, or within intracellular organelles such as the Golgi apparatus. ENTPDases play critical roles in modulating immune responses, inflammation, and neuroinflammation by controlling extracellular nucleotide availability in mammals. Moreover, they contribute to adenosine-mediated signaling in cooperation with 5’-nucleotidases (CD73). Pathogenic microorganisms also express ENTPDases, manipulating host purinergic signaling, suppressing adenosine triphosphate (ATP)-driven inflammation, and promoting immune evasion via increased adenosine production. Pathogenic parasites also express ENTPDases, manipulating host purinergic signaling, suppressing ATP-driven inflammation, and promoting immune evasion via increased adenosine production. Given their involvement in infection and inflammatory diseases, ENTPDases have emerged as promising pharmacological targets. This review comprehensively analyzes the ENTPDases from mammals and pathogenic parasites, emphasizing their role in purinergic signaling and their potential as therapeutic targets. While ENTPDase inhibitors hold promise for modulating inflammation and infection, their clinical translation faces challenges, including selectivity, off-target effects, and systemic alterations in purinergic homeostasis. Addressing these concerns through targeted drug delivery, allosteric modulation, and improved inhibitor specificity is crucial for therapeutic advancements. Review Wed, 28 May 2025 00:00:00 GMT IsadoraCunha Ribeiro, AmandaLaviola de Andrade, Vitóriade Almeida Rodrigues, MarksonSuarez Lacôrte Lima, JulianaLopes Rangel Fietto, Wed, 28 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100691 https://www.explorationpub.com/Journals/en/Article/100690 Aim: Natural products possess diverse pharmacological properties that are effective and safe for treating and managing amnesia; however, there is little or no scientific proof for most of their claims. This study evaluates the efficacy of Lecaniodiscus cupanioide-supplemented diets (LCSD) and Alchornea cordifolia-supplemented diets (ACSD) on scopolamine-induced amnesia in male rats. Roots of L. cupanioide and A. cordifolia were obtained and used to formulate 10% and 20% supplemented diets. Methods: Experimental animals were orally pre-fed LCSD and ACSD for 14 days before the induction of amnesia via single i.p. (intraperitoneal) administration of scopolamine (2 mg/kg body weight). Experimental animals were subjected to a Y-maze test to evaluate cognitive performance before experiment termination. The activities of hippocampal key enzymes linked to cognitive function were determined. Results: The result of the Y-maze showed that the induction of amnesia significantly (p < 0.001) reduced spatial memory function, which was protected against LCSD and ACSD pre-treated rats. Also, pre-treatment with supplemented diets inhibited the significant (p < 0.01) aggravation of monoamine oxidase, arginase, tumor necrosis factor-α, malonaldehyde, myeloperoxidase, acetylcholinesterase, and butyrylcholinesterase concentrations, and the significant (p < 0.05) depletion of dopamine, nitric oxide, interleukin-6, total thiol, and non-protein thiol concentrations, in comparison with that observed with amnesic-induced untreated rats. Comparatively, LCSD was more effective in preventing neuronal enzymatic imbalances, while ACSD was more effective in avoiding antioxidant status depletion. Conclusions: Conclusively, this study established that the supplemented diets possess potent anti-amnesic and neuroprotective abilities. Furthermore, this study recommends supplemented diets as a dietary intervention for preventing and managing amnesic conditions. Original Article Fri, 23 May 2025 00:00:00 GMT Odunayo MichaelAgunloye, Ayodele EbenezerAijo, Olamide WilsonFasakin, GaniyuOboh, Fri, 23 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100690 https://www.explorationpub.com/Journals/en/Article/100693 Alzheimer’s disease, the main cause of dementia worldwide, is a slowly progressive neurodegenerative disorder. This disease involves a diversity of etiophatogenic processes as it is not only a genetic but also a biological and environmental disease. Owing to that complexity, nowadays there is no efficacious treatment for this disorder. The major Alzheimer’s disease clinical indications include extracellular senile plaques of amyloid-β protein, intracellular hyperphosphorylated τ neurofibrillary tangles, uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. The evaluation of the neuroprotective potential of new compounds is imperative. As natural products, like phenolic compounds, exhibit several bioactivities, it is urgent to test them and evaluate their inhibition of each clinical indication of Alzheimer’s disease. If phenolic compounds target more than one Alzheimer’s disease pathogenic mechanism (multi-target drug ligands), they will have the potential of becoming a leading Alzheimer’s disease treatment. Thus, this review analyzes, for each Alzheimer’s disease clinical indication, the scaffolds of several phenolic compounds leading to the highest activity with the objective to find phenolic compounds active against all the clinical indications. It was concluded that compounds presenting scaffolds like rugosin E or isocorilagin show potential in combating Alzheimer’s disease. Review Fri, 06 Jun 2025 00:00:00 GMT JorgeMedeiros, Fri, 06 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100693 https://www.explorationpub.com/Journals/en/Article/100694 Not applicable. Editorial Fri, 06 Jun 2025 00:00:00 GMT RyszardPluta, Fri, 06 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100694 https://www.explorationpub.com/Journals/en/Article/100695 Spinal myelopathies, characterized by neurological deficits due to spinal compression in the spinal column, are increasingly common in the aging population. Although spinal myelopathies commonly present with sensory and motor deficits, they also manifest with life-debilitating enteric dysfunction associated with increased gastroparesis, constipation, bloating, abdominal pain, neurogenic bowel disease, and bladder and bowel incontinence. That said, the effects of spinal myelopathies on enteric gastrointestinal (GI) function are still poorly understood. This review aims to summarize existing literature concerning spinal myelopathies and their effect on the GI system, including the relevant anatomy and physiology of the nervous systems, etiology of various spinal cord injuries, clinical manifestations, current diagnosis and treatment strategies, and ongoing research concerning the gut-brain-spinal axis. The autonomic nervous system contributes to GI innervation through enteric reflex arcs and communication with the central nervous system (CNS) via spinal nerves. When spinal cord damage occurs, enteric reflex arcs, autonomic regulation, and gut-brain-spinal axis can become impaired, leading to GI symptoms. Etiologies of spinal myelopathies occur at all spinal levels. Spinal myelopathy includes inflammatory processes, such as multiple sclerosis and infection, and non-inflammatory processes, such as spondylosis, degenerative disc disease, tumors, and traumatic spinal cord injuries. Diagnosis modalities include imaging, particularly MRI, and functional assessments, such as high-resolution anorectal manometry and colonic transit studies. Enteric dysfunction treatment includes non-pharmacological, pharmacological, neuromodulatory interventions, and surgery. These strategies encompass lifestyle modifications, laxatives, prosecretory agents, 5HT4 agonists, vagus nerve stimulation, sympathetic nerve stimulation, colostomy, and ileostomy. Despite these treatment options, ongoing research with pudendal nerve stimulation, transanal irrigation, mesenchymal stem cells, and the relationship between the gut microbiome and gut-brain-spinal nerve axis may be beneficial in understanding spinal cord myelopathy-related enteric dysfunction, diagnosis, and treatment, ultimately improving clinical outcomes and quality of life for those who are affected. Review Tue, 17 Jun 2025 00:00:00 GMT MominAhmed, DianaFeier, LucaBertola, BrianKent, ChaseComprosky, ConnorRupp, BrandonLucke-Wold, Tue, 17 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100695 https://www.explorationpub.com/Journals/en/Article/100692 All living beings, from microorganisms to plants, animals, and humans, require iron as an essential micronutrient for their lives. However, iron overload can constitute a scenario prone to damage to the organism, including oxidative stress, deterioration of cellular and subcellular membranes, and thus leading to cell death. This process involves unrestricted lipid peroxidation caused by the generation of reactive oxygen species (ROS) because of an abrupt increase in free Fe2+ in the cytoplasm, all of which leads to subsequent membrane damage and iron-dependent cell death, now known as “ferroptosis”. This process can be induced by convulsive stress, and conversely, inducing seizures, and in both situations under a context of neuroinflammation. In this critical review, we will highlight the most relevant aspects of this recently described mechanism, which has been studied little in epilepsy, its impact on the prognosis of the disease, and its effects on the development of central and/or peripheral comorbidities, including SUDEP (sudden unexpected death in epilepsy). Mini Review Thu, 05 Jun 2025 00:00:00 GMT JerónimoAuzmendi, AlbertoLazarowski, Thu, 05 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100692 https://www.explorationpub.com/Journals/en/Article/100696 Depression is associated with executive cognitive deficits which are not well explored and treated. Such deficits have a significant impact on remission and recurrence. To understand the neurocognitive mechanisms of executive processes, a literature search was conducted using bibliographic databases in neuroscience and cognitive sciences: PubMed, ScienceDirect, EBSCOhost, and PsyArxiv, combining search terms: “depression”, “executive functions”, and “specific brain event-related potentials”. The theoretical review focuses on experiments using electrophysiological techniques, non-invasive tools with high temporal resolution. Depression shows alterations in brain activity linked with cognition: P3 diminished amplitudes and prolonged latencies, indicating executive attentional dysfunction; similar activity characterizes mismatch negativity (MMN), reflecting difficulties for change detection, voluntary effort, and mental shifting. Besides, depression tends to increase N1 latencies related with discrimination, and amplitudes of loudness dependence of auditory evoked potentials (LDAEP), suggesting inhibitory control’s deficits. Regarding feedback processing, the alterations of error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe), at anterior cingulate cortex (ACC), and frontal regions, are related with troubles for error awareness, cognitive control, and error monitoring in depression. Lastly, the ability to interpret coherently the information value of negative feedback (NF), and a propensity to commit perseverative and non-perseverative errors, need further investigation. Depressive individuals commit both errors on more occasions than controls, what seems to relate with fronto-striatal networks’ alterations, producing visual attention deficits and difficulties for inhibiting incoming information. Results show a variety of brain and executive cognitive components that are impaired under depression, although further research may clarify controversies resulting from depression heterogeneity and methodology used. Review Thu, 19 Jun 2025 00:00:00 GMT EloisaRuiz-Marquez, Thu, 19 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100696 https://www.explorationpub.com/Journals/en/Article/100698 Parkinson’s disease is typified by Lewy bodies and the selective death of dopaminergic neurons in the substantia nigra. α-Synuclein aggregation, neuroinflammation, mitochondrial dysfunction, and oxidative stress are key components of its pathophysiology. The neuroprotective potential of natural substances with anti-inflammatory and antioxidant qualities has drawn attention in recent years. A naturally occurring isoflavone that is mostly present in red clover and other legumes, biochanin A has shown promise as a treatment option for Parkinson’s disease. Preclinical research has shown that biochanin A uses a variety of methods to provide notable neuroprotective benefits. By activating the Nrf2/ARE pathway, it scavenges reactive oxygen species (ROS), upregulates antioxidant defense enzymes, and inhibits pro-inflammatory mediators by modifying the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling cascade. Additionally, it has been demonstrated that biochanin A preserves neuronal integrity in Parkinson’s disease models by reducing dopaminergic neuronal death, inhibiting microglial activation, and mitigating mitochondrial dysfunction. Its potential as a neurotherapeutic agent is increased by its capacity to pass the blood-brain barrier. To investigate its safety, bioavailability, and effectiveness in people, more translational and clinical research is necessary. Biochanin A’s incorporation with neuroprotective techniques may pave the way for novel supplementary treatments for Parkinson’s disease. Therefore, the current review aims to present a thorough investigation of the molecular basis of biochanin A’s anti-Parkinson properties in Parkinson’s disease, building on the body of existing research that explains these properties. Review Fri, 04 Jul 2025 00:00:00 GMT AmninderKaur, SimranKaur, AmirMushtaq, DikshaDalal, ShubhamKumar, AnishSingh, Fri, 04 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100698 https://www.explorationpub.com/Journals/en/Article/100699 Aim: Mutations in the EFHC1 gene have been identified in patients with various epilepsies, including juvenile myoclonic epilepsy (JME). Mice with Efhc1 deficiency also exhibit epileptic phenotypes. The protein myoclonin1, encoded by EFHC1, is not expressed in neurons but in cells with motile cilia, including choroid plexus and ependymal cells lining of brain ventricles. However, the molecular mechanisms by which EFHC1 mutations cause epilepsy remain unclear. Because of the involvement of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in epileptic phenotypes and the involvement of myoclonin1 in calcium ions (Ca2+) signaling, we investigated possible functional interplay between myoclonin1 and IP3R1. Methods: We performed immunohistochemical staining of brain tissues and co-immunoprecipitation assay of myoclonin1 and IP3R1, and Ca2+ imaging analyses using human HeLa.S3, mouse embryonic fibroblasts, or glial cells derived from Efhc1 homozygous knockout (Efhc1–/–) and wild-type (WT) littermates. Results: Myoclonin1 was revealed to be well co-expressed with IP3R1 at choroid plexus and ependymal cells, and these two proteins bound to each other. Endoplasmic reticulum (ER) of Efhc1-deficient mouse (Efhc1–/–) cells showed larger amounts of Ca2+ than that of WT mice, and IP3-induced Ca2+ release (IICR) from ER was higher in Efhc1–/– cells than that of WT. Furthermore, myoclonin1 was revealed to interact with beta subunit of glucosidase II (PRKCSH), also known as a protein kinase C substrate 80K-H, which interacts with IP3R1. Myoclonin1 further binds to IP3R2 and IP3R3. Conclusions: These results indicate that myoclonin1 modulates ER-Ca2+ homeostasis through interactions with IP3Rs and PRKCSH, and suggest that myoclonin1 dysfunctions cause impaired intracellular Ca2+ mobilization. Its relevance to the epileptic phenotypes of patients with EFHC1 mutations is now of interest. Original Article Thu, 10 Jul 2025 00:00:00 GMT ToshimitsuSuzuki, KripamoyAguan, HideakiMizuno, IkuyoInoue, KatsuhikoMikoshiba, AtsushiMiyawaki, KazuhiroYamakawa, Thu, 10 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/100699 https://www.explorationpub.com/Journals/en/Article/1006101 Not applicable. Editorial Thu, 24 Jul 2025 00:00:00 GMT GiustinoVarrassi, GiacomoFarì, Ameen A.Al Alwany, Matteo L.G.Leoni, Thu, 24 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006101 https://www.explorationpub.com/Journals/en/Article/1006104 Down syndrome (DS), caused by trisomy 21, is strongly associated with an increased risk of early-onset Alzheimer’s disease (AD). This work explores the cellular, genetic, epigenetic, and neuropsychological mechanisms that underlie the accelerated development of AD in individuals with DS. We review key contributors such as amyloid-β accumulation, mitochondrial dysfunction, oxidative stress, tau pathology, neuroinflammation, and chromosomal and epigenetic instability in the neuropathology of AD in DS. Particular attention is given to genes, microRNAs, and chromatin remodeling factors encoded by human chromosome 21 (Hsa21) that regulate these pathological processes. We also highlight the roles of non-coding RNAs and altered DNA methylation patterns in modulating gene expression and neuronal vulnerability. Additionally, the writing evaluates current pharmacological and non-pharmacological interventions and addresses the critical need for inclusive, person-centered health services. Integrating molecular biology with clinical perspectives, the review emphasizes the importance of early diagnosis and coordinated care strategies for individuals with DS at risk for AD. Review Wed, 06 Aug 2025 00:00:00 GMT OctavioGarcía, EduardoDomínguez-de-la-Cruz, Itzel GuadalupeLuna-Martínez, José AlfonsoGarnett-Carbajal, Jesús AntonioVillegas-Piña, Wed, 06 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006104 https://www.explorationpub.com/Journals/en/Article/1006102 Neurofibromatosis type 1 (NF1) is a hereditary, autosomal dominant condition marked by the development of tumors along the nervous system due to uncontrolled cell proliferation. The current case reports a 31-year-old male patient diagnosed with NF1 with the involvement of bilateral pheochromocytomas and colonic inflammatory polyps/leiomyoma. A genetic profile was explored through whole-exome sequencing to identify pathogenic variants, and segregation analysis was subsequently performed in the patient’s family. Sequencing analysis revealed a novel heterozygous frameshift variant, NF1 c.7301dupA (p.S2435Efs*11), which was identified as the pathogenic variant in the patient. Additionally, two identified variants, PMS2 c.2T>C (p.M1T) and MUTYH c.850-2A>G, may be associated with colonic tumor conditions in the patient. These findings provide insights into the molecular etiology underlying this rare presentation of multiple tumors in a Vietnamese male and may contribute to improved treatment planning and patient management. Case Report Mon, 28 Jul 2025 00:00:00 GMT Ha Thanh TranLe, Hai ThiTran, Linh KhanhNguyen, Lap TienDoan, Quyet Ngoc KieuLa, Thu HongNguyen-Huu, Ha HaiNguyen, Mon, 28 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006102 https://www.explorationpub.com/Journals/en/Article/1006103 Mucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo Syndrome type B, is a lysosomal storage disorder caused by mutations in the NAGLU gene, which encodes the enzyme alpha-N-acetylglucosaminidase, responsible for the degradation of heparan sulfate. Progressive accumulation of undegraded glycosaminoglycans primarily affects the central nervous system, resulting in severe neurodegeneration. Cellular findings reveal impaired intracellular trafficking, especially within the Golgi apparatus, linked to GM130 depletion and accumulation of GM2 and GM3 gangliosides. Endocytic vesicles fail to properly fuse with lysosomes due to genetic defects, disrupting lysosomal degradation. This contributes to oxidative stress, mitochondrial dysfunction, and mitophagy failure, which collectively drive neuronal apoptosis. MPS IIIB shares pathways with Alzheimer’s and Parkinson’s, suggesting cellular aging processes. Given the lack of specific treatment, modulation of inflammatory pathways such as TLR4 emerges as a potential therapeutic strategy. Commentary Mon, 28 Jul 2025 00:00:00 GMT Yorran Hardman AraújoMontenegro, Mon, 28 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006103 https://www.explorationpub.com/Journals/en/Article/1006105 Treatment resistant depression (TRD) is frequently encountered in clinical practice. The lack of response of the condition to conventional medications and augmentation strategies has spawned the search for novel treatment approaches. Psychedelic medications used in conjunction with intensive psychotherapy, so-called psychedelic-assisted psychotherapy (PAP), have been evaluated in a limited number of studies as an alternative tactic. This psychedelic renaissance has seen psilocybin, a naturally occurring, potentially hallucinogenic substance occurring in some species of mushrooms, used as one exemplar. The definition of “treatment resistance” varies between different authorities, but there is general agreement that a minimum standard is failure to respond to at least two pharmacological agents from different classes used at a therapeutic dose for an adequate length of time. In the studies to date, more stringent definitions have mostly been applied. Each of the clinical evaluations finds that the addition of a single dose of psilocybin to the psychotherapeutic regimen produces a rapid and clinically significant decline in depressive symptomatology, which is mostly retained in follow-up evaluations out to 12 weeks or longer. Psilocybin was well tolerated with mostly mild to moderate side effects of elevated blood pressure, fatigue, lack of concentration, headache, lethargy, vertigo, feeling of physical or emotional weakness, decreased appetite, nausea, feeling dull, and being easily exhausted, which were transient. Hallucinogen persisting perception disorder (HPPD) has occasionally been reported, while there were few reports of suicidal ideation and behaviour. Psilocybin appears to offer the promise of rapid alleviation of resistant depressive symptoms, but further controlled evaluations are necessary before the drug can be given routinely. Review Fri, 08 Aug 2025 00:00:00 GMT Trevor R.Norman, Fri, 08 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006105 https://www.explorationpub.com/Journals/en/Article/1006106 Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of Exploration of Neuroscience were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors. Perspective Wed, 13 Aug 2025 00:00:00 GMT Dirk M.Hermann, MarcoBacigaluppi, Claudio L.Bassetti, GabrioBassotti, JohannesBoltze, AndrewChan, TurgayDalkara, AdamDenes, ExuperioDiez-Tejedor, RichardDodel, Thorsten R.Doeppner, EgorDzyubenko, AymanElAli, TamasFulop, AlexanderGerhard, BerndGiebel, JanineGronewold, MatthiasGunzer, ThomasHeinbockel, KaibinHuang, MarcelloIriti, Hans-OttoKarnath, Kasteleijn-NolstTrenite, ErtugrulKilic, GiuseppeLanza, ArthurLiesz, Tim UllrichMagnus, JessicaMandrioli, AyanMohamud-Yusuf, ThomasMüller, SuyuePan, LucaPeruzzotti-Jametti, StefanoPluchino, RyszardPluta, AurelPopa-Wagner, AmenehRezayof, Mohamed L.Seghier, XinhuaShu, VikramSingh, JussiSipilä, MarkSlevin, YameiTang, GeorgiosTsivgoulis, GiustinoVarrassi, ChenWang, BayramYilmaz, Maha S.Zaki, JinweiZhang, Wed, 13 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006106 https://www.explorationpub.com/Journals/en/Article/1006107 Aim: This study aimed to assess the relationship between clinician adherence to International League Against Epilepsy (ILAE) management guidelines and seizure freedom in adult patients with epilepsy at a Mexican tertiary care center. Methods: This retrospective cross-sectional study analyzed 404 adult outpatients with epilepsy from an institutional database (January–October 2013). Data were collected on demographic characteristics, seizure types, diagnostic workup completeness, treatment regimens, weight-adjusted dosing, self-reported adherence, and seizure freedom (defined as being seizure-free for at least 3 months). Statistical analysis included chi-squared tests (χ2) for categorical variables and multivariate logistic regression to identify independent predictors of seizure freedom. Results: Of 404 patients analyzed (58.7% female, mean age 33 ± 13 years), 49.3% achieved seizure freedom. Generalized seizures (including primary and secondarily generalized seizures) were most common (66%), followed by focal seizures (30%). Diagnostic studies included an electroencephalogram in 80% and a magnetic resonance imaging scan in 75% of patients. Monotherapy was used in 50.7%, polytherapy in 44.6%, with weight-adjusted dosing achieved in 92%. Self-reported treatment adherence was 81%. Factors significantly associated with seizure freedom included treatment adherence (51.4% vs. 27.3% in non-adherent patients, χ2 = 13.56, p < 0.001), monotherapy vs. polytherapy (71.7% vs. 62.9%, χ2 = 46.07, p < 0.001), and adequate weight-adjusted dosing (44.9% vs. 32.3%, χ2 = 5.97, p = 0.01). Conclusions: Adherence to ILAE management guidelines, particularly regarding monotherapy selection, weight-adjusted dosing, and treatment adherence, was significantly associated with improved seizure freedom rates. These findings underscore the importance of implementing evidence-based epilepsy management protocols systematically in clinical practice. Original Article Fri, 15 Aug 2025 00:00:00 GMT Rodolfo CesarCallejas-Rojas, Héctor GerardoHernández-Rodríguez, IldefonsoRodriguez-Leyva, Fri, 15 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006107 https://www.explorationpub.com/Journals/en/Article/1006108 Aim: We previously observed oxidative stress and neuroinflammation caused behavioral and neurochemical changes in young Gabrb2 (gamma-aminobutyric acid type A receptor β2 subunit) knockout (KO) mice. Aging was moderated in a D-galactose-induced accelerated aging mouse model by an oral Chinese medicinal herbal formula BYPA consisting of Bupleurum chinense, Corydalis yanhusuo, Polygonum multiflorum, and Albizia julibrissin. The present study aimed to examine first whether Gabrb2-KO phenotypes observed in young adult mice would remain in aged mice, and whether BYPA may display a role of anti-aging in naturally aged mice. Methods: A range of behavioral tests were performed on naturally aged Gabrb2-KO and wild-type (WT) mice treated with BYPA. Oxidation stress level was evaluated by MDA (malondialdehyde) test, and the expressions of antioxidant enzymes (superoxide dismutase and catalase) were measured using RT-qPCR (reverse transcription-quantitative polymerase chain reaction). Results: Behavioral tests on aged Gabrb2-KO mice showed hyper-locomotor activity, social function deficit, decreased levels of anxiety and depression, consistent with a previous study on young Gabrb2-KO mice. Oral administration of BYPA ameliorated anxiety, activity, and depression. Remarkably, BYPA protected facial tissues with regrowth of significantly lost hairs and whiskers due to aging. It also reduced oxidative stress levels and enhanced the expression of antioxidant enzymes. Conclusions: The present study showed that schizophrenia-like behavioral changes were exhibited by aged Gabrb2-KO mice, similar to what was reported earlier, suggesting that the observed behavioral changes did not result from any developmental delay, but a direct result of Gabrb2-KO, reconfirming the critical role of Gabrb2 in schizophrenia etiology. Since the BYPA herbal formula moderated the oxidative status and enhanced the expressions of antioxidant enzymes in D-galactose-accelerated aging as well as naturally aged mice, it might furnish a useful health supplement to both the schizophrenic and the aged populations, due to its significant antioxidation and anti-inflammation effects exerted in the brain. Original Article Wed, 10 Sep 2025 00:00:00 GMT ManelBarki, AtaUllah, GanbolorSukhbaatar, Wai-kinMat, HongXue, Wed, 10 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006108 https://www.explorationpub.com/Journals/en/Article/1006109 Aim: Alzheimer’s disease (AD) is a chronic neurodegenerative brain dysfunction and the most common form of dementia, especially in the elderly, and is considered a serious problem for health systems worldwide. It is a multifactorial and progressive condition, characterized by memory loss, personality changes and decline in cognitive function, in addition to neuropsychiatric complications such as depression, anxiety, sleep disorders, and others, further reducing the quality of life of patients with AD. Since the introduction of galantamine in AD therapy, medicinal plants and herbal remedies are gaining increasing interest as complementary and alternative interventions and are a valuable source for the development of drug candidates for AD. This work aims to explore Tithonia diversifolia ethanol extract (EETD), which showed an acetylcholinesterase (AChE) inhibitory activity like rivastigmine, as a new candidate for molecular targets of AD. Methods: Mice were submitted to intracerebroventricular (I.C.V.) streptozotocin (STZ)-induced AD (2.5 mg/mL) and separated into different groups: sham, vehicle, rivastigmine (0.6 mg/kg), and EETD (0.1, 1.0, and 3.0 mg/kg). After AD induction, the animals were treated for 24 days and submitted to behavioral tests of memory, anxiety and depression. After the tests, the animals were sacrificed and the hippocampus was removed for assays of oxidative stress, AChE activity and markers of neuroinflammation. In vitro studies evaluated the effect of the extract on tau hyperphosphorylation, beta-amyloid (Aβ), and nitric oxide (NO) production. Results: EETD promoted a reduction in STZ-induced behavioral parameters of depression and anxiety, as well as reversed memory deficits. Biochemical assays revealed that EETD increased antioxidant defenses, as well as decreased levels of neuroinflammation markers. In addition, EETD partially inhibited Aβ production. Conclusions: The results together suggest that the plant exhibits therapeutic relevance in AD. However, studies are needed to identify the phytoconstituents responsible for such effects. Original Article Thu, 11 Sep 2025 00:00:00 GMT GraziellaMartins Guimarães, Camila AndréCazarin, Julia GalvanBernadina, HeloisaImmianovsky Eisendecker, Ana Carolinedos Santos, Ana PaulaDalmagro, MartinaHarle, Maria EduardaVieira, AngelaMalheiros, Valdir CechinelFilho, Min SungKo, Chung HyeonLee, So-YoungPark, Márcia Maria deSouza, Thu, 11 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006109 https://www.explorationpub.com/Journals/en/Article/1006110 Not applicable. Editorial Tue, 16 Sep 2025 00:00:00 GMT AyanMohamud Yusuf, Dirk M.Hermann, Tue, 16 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006110 https://www.explorationpub.com/Journals/en/Article/1006112 Schizophrenia (SZ) is a complex psychiatric disorder characterized by disruptions in cognition, perception, and behavior, contributing significantly to the global burden of psychiatric disorders and necessitating ongoing research into its pathophysiology, diagnosis, and treatment. This narrative review explores recent insights into SZ research, highlighting the genetic, neurochemical, and neurodevelopmental factors that contribute to the disorder. Emerging evidence underscores the dynamic interplay between neurotransmitter imbalances, particularly involving dopamine, glutamate, and gamma-aminobutyric acid (GABA), and neuroinflammation, oxidative stress, and immune dysregulation in the pathophysiology of SZ. Neuroimaging, clinical staging models, and multi-omics technologies have deepened our understanding of structural and functional brain abnormalities, identifying potential biomarkers for early detection and subtyping. This has refined diagnostic frameworks and informed precision psychiatry approaches. Advances in pharmacological treatments, including trace amine-associated receptor 1 agonists, glutamatergic modulators, psychedelics, and anti-inflammatory agents, offer new therapeutic possibilities beyond conventional dopamine antagonists. Novel targets, such as N-methyl-D-aspartate (NMDA) receptor modulation and neuroprotective strategies, are also being explored to address negative and cognitive symptoms. Additionally, non-pharmacological interventions, such as neuromodulation techniques, digital therapeutics, and psychosocial interventions, are promising complementary strategies. Digital phenotyping, machine learning (ML), and artificial intelligence (AI)-driven tools enable real-time symptom tracking, early risk prediction, and personalized care delivery. Despite these advancements, challenges remain in early diagnosis, treatment adherence, and equitable access to mental health care, particularly in low-resource settings. Therefore, addressing these barriers requires interdisciplinary collaboration, public health education, and the integration of scalable, culturally sensitive, and AI-based mental health innovations. Future research should prioritize multi-omics integration, longitudinal and transdiagnostic studies, biomarker validation, and the real-world implementation of personalized interventions to improve outcomes and quality of life for individuals living with SZ. Review Mon, 13 Oct 2025 00:00:00 GMT Tolutope AdebimpeOso, Olalekan JohnOkesanya, Uthman OkikiolaAdebayo, Khalifat BoluwatifeObadeyi, Shuaibu SaiduMusa, Mohamed MustafAhmed, Ayantunde KayodeAyankola, Adebimpe BusolaOgundele, Joseph OlaloluwaOso, GilbertEshun, Don EliseoLucero-Prisno, Mon, 13 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006112 https://www.explorationpub.com/Journals/en/Article/1006113 Cyclic vomiting syndrome (CVS) is a rare disorder in which stereotypical periods of intermittent nausea and vomiting last between hours and over a week. The disorder overlaps with migraine, and the current treatment recommendations follow those of migraine management. The current patient had experienced vomiting periods lasting up to a week since the age of two. Prophylactic amitriptyline had led to probably slightly longer intervals between CVS periods, while several medications had proven ineffective. At the age of 17, there was an excellent response to peroral olanzapine, which eventually proved sufficient to abort the vomiting periods in a single dose when taken at the beginning of one. In light of these and previously reported cases, early administration of olanzapine is suggested to treat CVS periods. Case Report Wed, 22 Oct 2025 00:00:00 GMT SaraSipilä, KirsiKallio, VirpiSidoroff, MarikaJantunen, Jussi O.T.Sipilä, Wed, 22 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006113 https://www.explorationpub.com/Journals/en/Article/1006114 Guillain-Barré Syndrome (GBS) is a rare cause of acute, flaccid paralysis and affects populations around the world, usually in the setting of recent gastrointestinal infection. The myelin sheaths of affected patients are destroyed, and consequently, the disease can manifest variably with the most common complaints including weakness, disturbances in sensation, and pain. Multiple available pharmacotherapies are employed to address disease progression and promote the reversal of symptoms. However, there is no widely accepted guideline detailing tiers of pain management options, despite pain being a significant primary complaint during the acute phase of the disease. To address this, we searched the GBS literature for publications that specifically discussed patient pain, how the pain was managed by the clinician, and how patients responded to various modalities. We discuss the findings of the literature review we conducted, evaluate the expansive list of existing options for treating pain and how they fared in symptom resolution, and draw conclusions based on our observations of which interventions addressed patient pain effectively and which were less successful. While general management of GBS, including treatment and efforts towards symptom reversal, has been robustly discussed in the literature, our work stresses the lack of research towards pain management in GBS and emphasizes the need to fill the gap in patient care for patients with this disease. Review Tue, 28 Oct 2025 00:00:00 GMT Kyla D.Groves, Alexander M.Preisig, AlexanderAldanese, KunalAggarwal, Tue, 28 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006114 https://www.explorationpub.com/Journals/en/Article/1006115 Aim: This study investigated the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on post-stroke outcomes, including quality of life, physical fitness, cognitive function, depression, and overall disability. Methods: The difference between Met carriers and non-Met carriers was analyzed for the entire sample and in pair-matched analysis, using age, sex, time since stroke, and race. Results: We evaluated 89 stroke participants (mean age, 57 ± 10 years; 58% male; 54% White, and 49% Hispanic). Twelve participants (13%) had one copy of the BDNF Val66Met (Val/Met heterozygotes) and none had two copies (Met/Met homozygotes). Comparing Met (n = 12) and non-Met carriers (n = 77), no significant differences were observed in demographics or clinical characteristics, including motor or cognitive outcomes. In pair-matched analysis, a significant difference was observed for the Center for Epidemiological Studies Depression (CES-D) scale, where Met carriers had significantly greater CES-D scores than non-Met carriers (24 ± 16 vs. 9 ± 9, p = 0.011). Regardless of the chosen CES-D cut-off scores (≥ 16 vs. ≥ 20), more cases of depressive symptomatology were observed among those with the BDNF Val66Met polymorphism than those without it (p values < 0.05). Conclusions: The BDNF Val66Met polymorphism may be associated with post-stroke depression but not motor or cognitive recovery. Original Article Tue, 11 Nov 2025 00:00:00 GMT EduardTiozzo, Gary J.Farkas, Lauren T.Shapiro, Liz J.Caldera, SebastianKoch, Clinton B.Wright, DavidLowenstein, TatjanaRundek, Tue, 11 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006115 https://www.explorationpub.com/Journals/en/Article/1006116 Background: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, with a poor prognosis despite advances in treatment options. T-cell-engager therapies, which have an antibody-based structure connecting immune cells to target cancer cells with high affinity, offer a promising strategy but face four key barriers: antigen heterogeneity, immune escape, the blood-brain barrier (BBB), and the immunosuppressive tumor microenvironment (TME). This systematic review synthesizes preclinical developments in bispecific T-cell engager (BiTE), tri-specific T-cell engager (TriTE), and multi-specific T-cell engagers for GBM over the last 10 years, evaluating their capacity to overcome these barriers. Methods: A systematic search was conducted in OVID Medline, Embase, and ClinicalTrials.gov for pre-clinical and clinical studies. A descriptive analysis without meta-analysis was formulated in which data were grouped thematically by the ability of treatments to overcome GBM-specific barriers. Results: Among the 14 studies meeting inclusion criteria, all studies were preclinical, with 12/14 (85.7%) utilizing an in vivo mouse model. BiTEs were used in 12/14 (85.7%) studies, while 4/14 (28.6%) studies targeted multiple antigens through either TriTEs or multivalent BiTEs. There was a range of antigen targets with the most common being interleukin 13 receptor alpha 2 (IL13Rα2) as well as epidermal growth factor receptor (EGFR) or EGFR variant III (EGFRvIII) in 7/14 (50.0%) studies. Most studies (85.7%) addressed two or more barriers, with 13/14 (92.9%) showing evidence of affecting the TME. Discussion: In the last decade, T-cell engager therapies have evolved in both antigenic targets and delivery vehicles used to overcome the key barriers. An emerging area within T-cell engager therapies is targeting multiple antigens through multi-specific T-cell engager therapies, such as the TriTEs. Studies have explored chimeric antigen receptor T-cells (CAR-Ts) as a potential delivery vehicle for BiTEs. A future clinical trial using multi-specific T-cell engager therapies or a CAR-T-secreting BiTE in adult patients is required to determine the potential clinical utility of T-cell engagers. Systematic Review Fri, 28 Nov 2025 00:00:00 GMT Adam H.Lapidus, MalakaAmeratunga, Fri, 28 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006116 https://www.explorationpub.com/Journals/en/Article/1006117 Primary central nervous system lymphoma is a rare form of extranodal non-Hodgkin lymphoma that is confined to the brain, spinal cord, leptomeninges, or eyes, representing less than one percent of all non-Hodgkin lymphomas and approximately four percent of primary brain tumors. When the disease is truly isolated to the central nervous system, with no evidence of systemic spread, it poses unique diagnostic and therapeutic challenges, particularly in immunocompetent patients. We reviewed nine recently published cases from 2021 to 2024 that described isolated primary central nervous system lymphoma without extracranial involvement. Patients ranged in age from forty-four to eighty-five years, with both immunocompetent and immunosuppressed individuals represented. Presenting symptoms include focal neurological deficits, seizures, progressive confusion, cranial neuropathies, and neurolymphomatosis. Magnetic resonance imaging findings were diverse, including intra-axial masses, leptomeningeal and cranial nerve enhancement, and mass effect. Cerebrospinal fluid analysis was variably positive for lymphoma cells. Histopathological analysis confirmed diffuse large B-cell lymphoma in all cases, although initial biopsies were sometimes inconclusive, underscoring the importance of repeat tissue sampling and expert pathology review. Treatment strategies most often included high-dose methotrexate-based chemotherapy, monoclonal antibody therapy, and radiotherapy, with some patients undergoing surgical decompression or diagnostic craniotomy. Follow-up data revealed variable survival outcomes, with a subset of patients achieving disease-free survival beyond one year. These cases highlight the wide clinical spectrum and diagnostic complexity of isolated primary central nervous system lymphoma and reinforce the need for a high index of suspicion, timely advanced imaging, multidisciplinary discussion, and appropriate tissue diagnosis to guide individualized management. Case Report Tue, 02 Dec 2025 00:00:00 GMT AliMsheik, MuathHussein, AlaaeldinAhmed, AiyatMohamed, Abbas F. AbdulHussein, HayelSalih, KazimMohammed, AbdelnaserThabet, Tue, 02 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006117 https://www.explorationpub.com/Journals/en/Article/1006118 Neurological disorders constitute a major global health burden with limited effective treatments. Despite advances in molecular neuroscience, critical gaps persist in understanding intercellular communication systems underlying central nervous system homeostasis and neurodegeneration. Extracellular vesicles (EVs), nanoscale to microscale membrane-bound vesicles secreted by virtually all cell types, have emerged as pivotal mediators of intercellular communication in neurological pathologies. This review examines molecular mechanisms governing EV biogenesis, cargo selection, and pathological functions in neurological disorders, emphasizing the emerging role of ubiquitin-like protein 3 (UBL3) as a novel regulator of EV-mediated protein sorting. Neural cell populations produce specialized EV subtypes containing distinct molecular cargo reflecting their physiological states. UBL3, a membrane-anchored post-translational modifier, operates through geranylgeranylation-dependent mechanisms to promote selective protein incorporation into small EVs (sEVs), with knockout studies demonstrating approximately 60% reduction in EV protein content. Proteomic analyses reveal UBL3 interacts with over 1,200 proteins, with ~30% classified as EV cargo proteins. Critically, UBL3-mediated sorting influences disease-associated protein trafficking, including α-synuclein in Parkinson’s disease and mutant huntingtin in Huntington’s disease, suggesting involvement in prion-like spreading mechanisms. EVs’ dual nature as pathological mediators and therapeutic vehicles represents a paradigm shift in neurological medicine. EVs offer advantages as natural drug delivery systems capable of crossing the blood-brain barrier, accessible biomarkers for noninvasive disease monitoring via liquid biopsies (achieving diagnostic accuracies exceeding 0.88 ROC-AUC), and engineered therapeutic platforms for delivering CRISPR-Cas9 systems and neuroprotective factors. However, clinical translation requires addressing challenges, including standardizing isolation protocols, elucidating cell-type-specific cargo sorting mechanisms, and defining optimal administration routes. Understanding UBL3-mediated cargo sorting mechanisms presents promising therapeutic opportunities by selectively modulating pathogenic protein trafficking. EVs, positioned at the intersection of pathogenesis and therapy, represent attractive targets for precision medicine approaches in neurological conditions, with UBL3 emerging as a novel molecular handle for manipulating EV composition and function. Review Tue, 02 Dec 2025 00:00:00 GMT Mst. AfsanaMimi, Md. MahmudulHasan, Tue, 02 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006118 https://www.explorationpub.com/Journals/en/Article/1006119 Although addiction is a complex and contextually embedded disorder that extends beyond individual pathology and neurobiological dysfunction, prevailing computational and clinical models often reduce addiction to a chronic brain disease. While such frameworks have shaped dominant approaches to treatment and theory, they remain poorly aligned with the lived experience and behavioral phenomena of addiction, ignoring its psychological, social, and systemic dimensions. This paper examines the limitations of various disease and compulsion models both critically and in-depth, highlighting their empirical and conceptual shortcomings. In doing so, it argues for the development of context-sensitive and psychologically grounded computational models, ones capable of capturing the nuanced realities of addiction and informing more effective, personalized interventions. Review Tue, 09 Dec 2025 00:00:00 GMT Anamaria MadelieneManu, Tue, 09 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006119 https://www.explorationpub.com/Journals/en/Article/1006120 Neurogenetic disorders remain genetically uncharacterized in many populations, including Libya. We report three Libyan patients from two consanguineous families with pathogenic variants in sodium channel genes. Two adult sisters (Patients 1 & 2) presented with global developmental delay and progressive spastic paraparesis without epilepsy. Whole exome sequencing identified the same heterozygous SCN8A variant (c.142G>A; p.Asp48Asn) in both sisters, classified as a variant of uncertain significance (VUS). Its occurrence in two affected siblings with a consistent phenotype and the absence of other explanatory variants provide supporting evidence for its potential pathogenicity. These cases represent the first documented instances of a suspected SCN8A-related disorder in Libya. A third, unrelated 10-year-old boy (Patient 3) with a phenotype consistent with Dravet syndrome, including refractory seizures and neurodevelopmental regression, was found to harbor a likely pathogenic heterozygous SCN1A variant (c.2113del; p.Glu705Lysfs*10). This report expands the genetic and phenotypic spectrum of neurological disorders in Libya and underscores the critical role of genetic testing, while also highlighting the need for segregation studies to achieve a definitive molecular diagnosis. Case Report Wed, 24 Dec 2025 00:00:00 GMT Anwaar M.Bennour, Ashraf M.Rajab, Heba A.El-Zawawi, Wed, 24 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006120 https://www.explorationpub.com/Journals/en/Article/1006121 Cerebral amyloid angiopathy (CAA), characterized by amyloid β deposition in cerebral vasculature, is increasingly recognized as a major contributor to both cognitive decline and lobar intracerebral hemorrhage (ICH) in older adults and often coexists with Alzheimer’s disease (AD). Understanding CAA is a crucial step for improving health outcomes and the development of effective therapies. However, significant gaps remain in our understanding of CAA’s pathophysiology, diagnostic approaches, biomarker development, and clinical management. A comprehensive review is therefore essential to synthesize existing knowledge and highlight key directions for future research. This review goes beyond prior summaries by critically synthesizing recent evidence on diagnostic innovations—including the Boston criteria v2.0 and emerging plasma biomarkers—and addressing pressing clinical dilemmas such as anticoagulation management in patients with coexisting atrial fibrillation and CAA. It also highlights ongoing research into multimodal diagnostic frameworks and precision treatment strategies aimed at bridging current diagnostic and therapeutic gaps. Together, these updates underscore how advancing biomarker validation, individualized risk stratification, and amyloid-targeted approaches may shape future CAA management and prevention. Review Mon, 05 Jan 2026 00:00:00 GMT TrinityWillsey, CharlesFaselis, AliAhmed, Mo-KyungSin, Mon, 05 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006121 https://www.explorationpub.com/Journals/en/Article/1006122 Flavonoids are a large class of natural polyphenolic substances ubiquitously synthesized in the plant kingdom. When entering the human body, these compounds can exert a wide range of biological activities, including immunomodulatory, antiinflammatory, and anticancer effects. Over the recent years, the mechanisms underlying these actions have become increasingly clear, also indicating the important involvement of G protein-coupled receptors (GPCRs), such as adenosine receptors, in signal transduction networks. In this perspective article, the potential role of flavonoids as adenosine receptor antagonists on the development, progression, and spread of glioblastoma is discussed, blocking the tumor-promoting and immunosuppressive actions of elevated levels of endogenous adenosine. Therefore, flavonoids can be considered as structural leads for developing novel antiglioblastoma agents, applied either alone or as boosters of chemo- or immunotherapy to improve the quality of life and outcome of patients. The importance of these studies is, in turn, emphasized by the current lack of effective treatment strategies for this highly aggressive and fast-growing brain tumor, associated with poor prognosis. Perspective Fri, 23 Jan 2026 00:00:00 GMT KatrinSak, Fri, 23 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006122 https://www.explorationpub.com/Journals/en/Article/1006123 Aim: Male infertility resulting from neurological disorders, oxidative stress, and hormonal imbalance is a growing health concern. This study, therefore, investigated the effects of Aframomum melegueta and Aframomum danielli-supplemented diets on sperm quality and testicular oxidative damage in a scopolamine-induced rat model. Methods: Adult male rats were randomly allocated into seven groups: normal group; scopolamine-induced group; donepezil-treated scopolamine group and four treatment groups receiving 4% or 8% dietary supplementation of Aframomum melegueta or Aframomum danielli, respectively. Sperm motility, count, and morphology were evaluated. In addition, serum testosterone and follicle stimulating hormone levels, testicular oxidative stress markers, inflammatory cytokines, and antioxidant activities were assessed to determine reproductive and biochemical responses. High performance liquid chromatography (HPLC) profiling was also conducted to identify the major phenolic compounds in both seeds. Results: Scopolamine administration impaired sperm quality, decreased hormonal levels, promoted oxidative stress, and altered inflammatory responses. These alterations were, however, reversed by diets supplemented with Aframomum melegueta and Aframomum danielli in a dose-dependent manner. The 8% supplementation produced better outcomes than 4% supplementation and donepezil treatment in most parameters, indicating protective effects on sperm quality and other reproduction-related indices. HPLC profiling revealed bioactive compounds that may collectively account for the observed restorative effects of the seeds. Conclusions: These findings demonstrate that Aframomum melegueta and Aframomum danielli seeds effectively reversed the adverse reproductive alterations caused by scopolamine-induced neurotoxicity. Both species significantly improved sperm quality and testicular function, which may suggest their possible development as plant-based nutraceuticals for protecting male reproductive health in future studies. Their phytochemical abundance further supports their potential as plant-based nutraceuticals. Original Article Mon, 02 Feb 2026 00:00:00 GMT Odunayo M.Agunloye, Esther A.Olawuyi, Ismail A.Oguntade, Seyi O.Aleruwa, GaniyuOboh, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006123 https://www.explorationpub.com/Journals/en/Article/1006124 Aim: Tissue transglutaminase [transglutaminase 2 (TG2)] is implicated in central neuronal apoptosis and is expressed in the peripheral nervous system; however, its role in sensory neuron survival and neuropathic pain after nerve injury remains poorly defined. This study examined whether TG2 knockout (KO) affects dorsal root ganglion (DRG) neuron survival and pain-related behaviors following sciatic nerve injury. Methods: TG2 KO mice and wild-type (WT) controls underwent complete sciatic nerve transection (axotomy). Pain-related behavior was evaluated using detailed autotomy scoring over 14 days. DRG neuron survival was assessed using unbiased stereological counts. Results: TG2 KO resulted in a distinct, previously unreported “atypical autotomy” pattern, with lesions localized mainly to the midplantar paw region. In contrast, WT mice exhibited typical autotomy directed primarily at the toes. Despite this clear difference in pain phenotype, stereological analysis revealed that TG2 KO did not alter neuronal counts in intact or axotomized DRGs, with both groups showing comparable, significant neuronal loss after injury. Conclusions: These findings indicate that TG2 functions as an important modulator of neuropathic pain but is not required for neuronal survival in the adult DRG following nerve injury. Original Article Thu, 05 Feb 2026 00:00:00 GMT Gong-WeiLyu, Xu-QiangPan, LiangHan, Xiao-HongMa, ChuangLyu, Tie-Jun StenShi, Thu, 05 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006124 https://www.explorationpub.com/Journals/en/Article/1006125 Not applicable. Retraction Mon, 09 Feb 2026 00:00:00 GMT Mst. AfsanaMimi, Md. MahmudulHasan, Mon, 09 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006125 https://www.explorationpub.com/Journals/en/Article/1006126 Hydrocephalus is a complex neurological disease characterized by abnormal cerebrospinal fluid (CSF) accumulation, ventricular enlargement, and progressive neurologic dysfunction. Existing therapies are predominantly surgical, with high complication rates, with high complication rates, prompting ongoing efforts to develop alternative modalities. This review integrates developments across mechanistic platforms and integrated disease models—including genetic and induced animals, patient-derived organoids, and organ-on-a-chip systems—to evaluate their ability to recapitulate CSF kinetics and subventricular zone (SVZ) biology. New therapies, including surgical enhancements, drugs, stem cell-based repair, and gene-targeted therapies, are discussed for translation potential. Ethics and regulatory frameworks, 3Rs, and validation and scalability issues are discussed critically. Finally, computational modeling and AI are introduced as ways to integrate multi-scale data and enable precision medicine. Each of these perspectives outlines a roadmap in which bioengineering, precision medicine, and ethical rigor converge to accelerate discovery and improve outcomes for patients with hydrocephalus. Review Tue, 10 Mar 2026 00:00:00 GMT IoannisAngelopoulos, Tue, 10 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006126 https://www.explorationpub.com/Journals/en/Article/1006128 Adult human hippocampal neurogenesis has been debated for decades, with methodological differences producing conflicting reports. Radiocarbon birth-dating provided population-level evidence of sustained dentate gyrus neuron turnover, while immunohistochemical studies produced variable results depending on fixation protocols. Optimized post-mortem handling has reported higher detectability of immature-neuron markers across adulthood, whereas longer post-mortem delays and prolonged fixation can reduce signal and contribute to apparent null findings; however, marker-based interpretations remain debated and require cautious, multi-marker validation. Recent single-nucleus and spatial transcriptomics further support persistent neurogenesis, identifying immature granule-cell signatures and niche programs into late life. This article critically appraises evidence from radiocarbon dating, immunohistochemistry, and transcriptomics, highlighting sources of discrepancy and convergence. Practical standards for human tissue handling, antigen retrieval, and multimarker panels are proposed to minimize methodological artefacts. Collectively, convergent evidence favors low-level, lifelong neurogenesis with potential contributions to memory precision and affective regulation, albeit at lower rates than rodents. It is concluded that integrating radiocarbon baselining, optimized immunohistochemistry, and transcriptomic validation provides a robust framework for resolving the controversy and advancing translational relevance in cognition, aging, and psychiatry. Review Tue, 17 Mar 2026 00:00:00 GMT MariaLoumpourdi, Tue, 17 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006128 https://www.explorationpub.com/Journals/en/Article/1006127 The circadian clock orchestrates cellular physiology by synchronizing transcriptional, metabolic, and signaling networks with the environmental light-dark cycle. Basic helix-loop-helix ARNT-like protein 1 (BMAL1), a core transcriptional regulator of circadian timing, contributes to rhythmic gene expression and is implicated in cellular responses to stress and energy demand. Emerging evidence suggests an interplay between BMAL1 and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, a central hub controlling cell survival, metabolism, and angiogenesis. In ischemic conditions, BMAL1 is associated with increased PI3K/AKT activity and downstream mTOR signaling, which may help preserve mitochondrial integrity, limit oxidative stress, and support neuronal and vascular recovery. Conversely, BMAL1 deficiency is linked to impaired AKT phosphorylation and redox imbalance, exacerbating ischemic injury. Proteomic and functional studies further suggest that BMAL1 may contribute to metabolic reprogramming through PI3K/AKT-dependent regulation of oxidative phosphorylation and antioxidant defenses. This review is based on a focused narrative evaluation of experimental and translational studies retrieved from PubMed, emphasizing circadian regulation of PI3K/AKT signaling in ischemic and vascular contexts. Collectively, these findings support the concept that BMAL1 functions as a temporal modulator of PI3K/AKT signaling, integrating circadian and metabolic cues to promote cellular resilience. Understanding this regulatory axis may offer novel therapeutic perspectives for ischemic and neurovascular disorders associated with circadian misalignment. Review Tue, 17 Mar 2026 00:00:00 GMT Mustafa C.Beker, Dirk M.Hermann, ErtugrulKilic, Tue, 17 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006127 https://www.explorationpub.com/Journals/en/Article/1006129 Chronic pain, defined as pain persisting beyond 12 weeks, is known to be challenging to manage. Despite increasing opioid prescribing, pain is still an issue for many patients. Patient education has emerged as a key element in supporting self-management and improving pain-related outcomes. This narrative review explores the impact of patient education alongside pain management interventions, with a focus on pain intensity, pain-related beliefs, and pain-related disability. A structured search using PubMed, Medline, EBSCOhost, and UCL Explore identified ten studies (six RCTs, two systematic reviews, two cohort studies) and three national guidelines meeting the inclusion criteria. Inclusion criteria focused on adult patients with chronic non-malignant pain who received some form of education alongside or prior to pain interventions. Pain education was associated with 29% reduction in opioid use, with 7% patients discontinuing opioids entirely in the usual group. Improvements in emotional functioning (41%), pain understanding (75%), and overall functioning (38%) were observed across various trials. Existing research shows promising results; however, the clarity of the type of education needed needs to be established. Short, focused education sessions, especially those incorporating pain neuroscience education (PNE) or cognitive behavioural therapy (CBT) elements, were as effective as longer programs. Further research is required to identify how education improves the outcome of pain management interventions. Integrating targeted patient education into the chronic pain care pathway can significantly reduce disability, improve quality of life, and decrease opioid reliance. These findings support implementing structured education sessions as part of routine pain management services to enhance long-term patient outcomes. Review Wed, 18 Mar 2026 00:00:00 GMT Kate ElizabethTordoff, RomanCregg, AlkistiGiannaki, MohamedHassouna, Wed, 18 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006129 https://www.explorationpub.com/Journals/en/Article/1006130 Malignant tumors of the nervous system, such as gliomas, medulloblastomas, and neuroblastomas, pose a greater clinical challenge due to their aggressive and invasive nature and their resistance to current treatment options. The blood-brain barrier (BBB) impairs the delivery of therapeutic agents, which is associated with poor prognosis. The natural flavonoid fisetin has demonstrated potential for cancer treatment by regulating major cancer-related signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK. Preclinical studies suggest that fisetin induces apoptosis, suppresses tumor invasion, and reduces malignancy in glioma, medulloblastoma, and neuroblastoma models. However, evidence for fisetin’s effectiveness remains preclinical and in vitro, with no clinical trials in humans to date. One solution to this challenge is to use nanotechnology-based delivery systems to increase fisetin’s stability and solubility and facilitate its crossing of the BBB, thereby enhancing its therapeutic efficacy. Such advancements have made fisetin a promising option for neuro-oncology treatment. Further clinical trials are needed to assess the safety, efficacy, and effectiveness of fisetin in combination therapies. When conjugated with nanotechnology-based delivery, fisetin may enable a digital transformation in treatment outcomes for patients with malignant nervous system tumors. Review Mon, 23 Mar 2026 00:00:00 GMT AjayKumar, Amita, Mon, 23 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006130 https://www.explorationpub.com/Journals/en/Article/1006131 Human behavior depends on a collection of cognitive capacities that are expressed with complexity in humans. Although animal models have been essential for identifying fundamental neural mechanisms, many aspects of human cognition require direct investigation in the human brain. Studies of social decision-making, communication, and spatial navigation increasingly rely on intracranial electrophysiology to probe the neural basis. Related to these topics, reward processing warrants emphasis. It is not uniquely human, but it provides a central organizing signal linking motivation, learning, emotion, and choice across many human behaviors. Disruptions of reward circuits are a hallmark of numerous neurological and psychiatric conditions, giving this domain specific relevance for patient care. Fifteen studies published between 2009 and 2024 used human intracranial recordings to examine reward-related processes, nearly all in patients undergoing invasive monitoring for drug-resistant epilepsy. These studies investigated 17 neocortical and subcortical regions, most frequently the orbitofrontal cortex, using intracranial EEG, deep brain stimulation, and single-unit recordings. Recent work increasingly incorporates social interactions and computational models of learning. The purpose of this narrative review is to provide an overview of human reward processing, emphasizing how intracranial recordings have clarified the neural circuits that underlie a range of human cognitive capacities. Beyond advancing basic neuroscience, intracranial electrophysiology can inform circuit-guided interventions for neurological and psychiatric disorders. Review Thu, 26 Mar 2026 00:00:00 GMT Ai Phuong S.Tong, Thu, 26 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006131 https://www.explorationpub.com/Journals/en/Article/1006132 There is a growing appreciation of the role of mitochondria in determining the interactions of CNS astrocytes, microglia, and neurons. The influence of circadian and systemic processes in regulating these interactions is relatively underexplored. Recent work has indicated the importance of night-time dampening and resetting in the pathoetiology of a diverse array of aging-associated medical conditions, including neurodegenerative disorders. The 10-fold decrease in pineal melatonin at night between childhood and the 9th decade of life is a major determinant of how aging associates with neurodegenerative disorders, cardiovascular disorders, and a wide range of tumors. It is proposed that the beneficial effects of pineal melatonin are mediated via its upregulation of the mitochondria-derived peptides (MDPs), including humanin. Although potentially induced in all mitochondria-containing cells, humanin is primarily produced in the CNS by astrocytes. The capacity of pineal melatonin to increase astrocyte humanin leads to the induction of the local melatonergic pathway in microglia to shift microglia from a pro-inflammatory M1-like to prophagocytic M2-like phenotype. In neurons, astrocyte-derived humanin optimizes mitochondrial function and decreases oxidant production to increase function and survival, possibly also involving mitochondrial melatonergic pathway upregulation. Concurrent effects of pineal melatonin in decreasing gut dysbiosis/permeability and stimulating oxytocin to activate the vagal nerve contribute to more optimized dampening and resetting that influences CNS interactions of glia and neurons. Overall, the conceptualizations of how astrocyte, microglial, and neuronal mitochondria interact require integration with wider circadian and systemic processes. A plethora of novel research implications are highlighted. Review Wed, 15 Apr 2026 00:00:00 GMT GeorgeAnderson, Wed, 15 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006132 https://www.explorationpub.com/Journals/en/Article/1006133 Major depressive disorder (MDD) is increasingly understood as a multifactorial psychiatric disorder involving interacting neural, immune, metabolic, and microbial processes. Within this framework, the microbiota–gut–brain axis and mitochondrial bioenergetics have emerged as potentially intersecting contributors to depressive symptomatology. Preclinical studies suggest that microbial metabolites—especially short-chain fatty acids (SCFAs)—can influence oxidative phosphorylation, redox balance, neuroinflammation, and synaptic plasticity, whereas inflammatory signals such as lipopolysaccharide may disrupt mitochondrial dynamics. However, the strength of evidence is uneven: mechanistic support is strongest in cell and animal models, whereas human data remain heterogeneous and largely associative. This narrative review critically synthesizes current evidence on microbiota–mitochondria crosstalk in MDD, distinguishing established findings from emerging hypotheses. It also examines recent psychobiotic trials, metabolomic and biomarker studies, and microglia–mitochondria mechanisms, and discusses the translational limitations that currently constrain clinical application. Overall, this axis represents a plausible and clinically relevant framework for hypothesis generation and adjunctive intervention development, but it should not yet be regarded as a fully validated causal pathway or stand-alone therapeutic target in MDD. Review Tue, 21 Apr 2026 00:00:00 GMT Oluwagbenga MayowaAdu, Chinonso AnitaChukwu, Oluwafunmbi EbenezerOgunmiluyi, Omolola ComfortAregbesola, Olamide DavidAwonowo, Shukurat JoyAjenikoko, Tue, 21 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006133 https://www.explorationpub.com/Journals/en/Article/1006134 Aim: Redox-oxidative dysregulation is implicated in the aetiology of several diseases, including schizophrenia, with a possible influence on clinical symptoms. This study investigated the influence of redox, lipid peroxidation, and micronutrient antioxidants on the expression of clinical phenotypes of schizophrenia. Methods: A total of 220 consenting drug-naïve volunteers, including 120 participants with schizophrenia and 100 apparently healthy controls, were recruited. Schizophrenia symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Lipid peroxidation (malondialdehyde; MDA) was quantified using the thiobarbituric acid reactive substances (TBARS) spectrophotometric method; glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were assessed using established enzymatic activity assays; total antioxidant capacity (TAC) was determined by the phosphomolybdenum colorimetric method; vitamins C and E were measured using spectrophotometric biochemical assays; and zinc (Zn) and selenium (Se) concentrations were quantified using atomic absorption spectrophotometry (AAS). Results: Enzymatic antioxidants, SOD (19.58 ± 0.80; 10.12 ± 0.45 U/L) and CAT (41.73 ± 1.81; 21.33 ± 0.98 U/L), increased in schizophrenia compared with controls (p < 0.05), but decreased non-enzymatic antioxidants; GSH (14.5 ± 0.28; 15.9 ± 1.59 µmol/L, p < 0.05). Furthermore, serum levels of zinc (1.8 ± 0.01; 2.7 ± 0.02 mg/L), selenium (0.08 ± 0.01; 0.10 ± 0.01 mg/L), and vitamin C (12.98 ± 0.49; 15.08 ± 0.37 mg/L) were lowered in schizophrenia compared with controls (p < 0.05). GSH had a negative correlation with positive symptoms (r = –0.285, p = 0.013) while SOD (r = 0.281, p = 0.001) and CAT (r = 0.179, p = 0.034) correlated positively with MDA (p < 0.05). In contrast, GSH (r = –0.247, p = 0.003) and TAC (r = –0.221, p = 0.009) correlated negatively with MDA (p < 0.05). Conclusions: Drug-naïve Nigerian individuals with schizophrenia appear to exhibit a pattern of redox imbalance, including increased lipid peroxidation, altered antioxidant enzyme activity, and reduced non-enzymatic antioxidants, with lower GSH levels modestly associated with greater positive symptom severity. Original Article Mon, 27 Apr 2026 00:00:00 GMT Tolutope AdebimpeOso, Sunday JoshuaAdeleye, Bamidele MusaSikiru, Babatunde WasiuGaniyu, Olarotimi AlexanderOwolagba, Olalekan JohnOkesanya, AdegboyegaOgunwale, Joseph DadaAdeyemi, OluyemiAkinloye, Mon, 27 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006134 https://www.explorationpub.com/Journals/en/Article/1006135 Aim: Stroke represents a leading cause of mortality and disability globally, yet comprehensive epidemiological analyses for Saudi Arabia remain limited. This study aimed to analyze temporal trends in stroke incidence, mortality, and disability-adjusted life years (DALYs) in Saudi Arabia from 1990 to 2021, examine stroke subtype distributions and risk factor attributions, and compare findings with regional and international benchmarks. Methods: We conducted a comprehensive analysis of the Global Burden of Disease (GBD) 2021 study data for Saudi Arabia, supplemented by systematic review findings and hospital-based registry data. Age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates were extracted for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Annual percent change (APC) was calculated using Joinpoint regression. Risk factor attribution was analyzed using comparative risk assessment methodology. Poisson regression models examined sex differences. Results: The pooled annual stroke incidence in Saudi Arabia was 29 per 100,000 population (95% CI: 15–47). Ischemic stroke predominated, comprising 79–87% of cases. Age-standardized DALYs showed significant yearly decreases of 9.28 per 100,000 (95% CI: 6.31–12.26, p < 0.001). The age-standardized death rate in the Middle East and North Africa (MENA) region was 87.7 per 100,000 [95% uncertainty interval (UI): 78.2–97.6] in 2019, representing a 27.8% regional decrease from 1990. Mean age at first stroke in Saudi Arabia was 63 years—six years younger than Western populations. Hypertension (57.7%), diabetes mellitus (49.4%), and obesity (42.0%) were the major modifiable risk factors. Intravenous thrombolysis utilization remained critically low at 1–3.6%. Conclusions: Despite declining mortality and DALYs, Saudi Arabia faces a substantial stroke burden characterized by a younger onset age and significant treatment gaps. Achieving Vision 2030 health targets requires accelerated primary prevention addressing metabolic risk factors and expansion of acute stroke treatment capacity nationwide. Original Article Mon, 27 Apr 2026 00:00:00 GMT Ahmed AbdulazizAlmohammadi, Mon, 27 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006135 https://www.explorationpub.com/Journals/en/Article/1006136 For this review paper, data on protein misfolding and aggregation in progressive myoclonus epilepsies and some developmental encephalopathies are gathered. There is evidence that in some cases of monogenic epilepsies, misfolding of the mutated protein takes place, often leading to protein aggregation. On one hand, protein aggregation reduces the amount of protein and its activity; on the other, it exerts generic toxicity to neurons. Understanding the molecular causes due to loss of normal function and gain of toxic function of the mutated aggregate-prone proteins is important to obtain new therapies. By observing the symptomatology of progressive and developmental epileptic syndromes, one can derive some conclusions about the relevance of protein misfolding and aggregation in the picture. A plausible view seems that the most severe symptoms of dementia, behavioral and psychiatric symptoms, are linked to protein aggregation and downstream effects on cellular degradation and energy systems. Finally, I discuss the potential of targeting the proteostasis network to develop novel anti-seizure and neuroprotective therapies. Review Sat, 09 May 2026 00:00:00 GMT EvaŽerovnik, Sat, 09 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006136 https://www.explorationpub.com/Journals/en/Article/1006137 Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention for its neuroprotective properties, especially for Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder with limited therapeutic options. This review provides several experimental evidence on the effects of TQ in AD models. The evidences indicate that TQ reduces the amyloid-β accumulation, reduces the oxidative stress and neuroinflammation, and improves cognitive and behavioral outcomes. Additionally, TQ should be able to promote the neuronal survival and neurogenesis while reducing biological markers that indicate brain damage or neuron loss. Although these findings clearly highlight and show the promising therapeutic potential of the TQ molecule in the AD, it is important to note that further in-depth studies are still needed to fully understand its underlying molecular mechanisms and to determine its clinical relevance in patients. Review Fri, 15 May 2026 00:00:00 GMT Jamil A.Chahrour, MarwaRammal, ZaherAbdel Baki, AkramHijazi, Fri, 15 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/en/Article/1006137