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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.