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.

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.

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.

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.

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.