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].

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.