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.

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.

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.

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.

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.

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.

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.

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.

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.