Neurological Disorders Research Articles

BRAIN COMPUTER INTERFACE: THE IMPACT ON NEUROPLASTICITY AND MOTOR LEARNING-A NARRATIVE REVIEW.

Background: Neurological disorders, especially stroke, have now become the major causes of death all around the world. They are also the leading cause of impairments and disabilities among those who survive which leads to dependency in ADL’s and an impairment in overall quality of life. Even though traditional rehabilitation techniques and advances in technology (VR/AR/GAMING/ASSISTIVE DEVICES/EXOSKELETONS) play a major role in the recovery process, not all individuals show a 100% positive outcome. Research suggests that the combination of BCI with traditional rehab techniques or advanced technologies help in increasing neuroplasticity by translating the brain signals into commands that can control external devices thereby leading to improved functions and activities. Objective: The objective of this review is to summarize the available evidence and to highlight the mechanism through which the BCI’s promote neuroplasticity and enhance motor functions. Methods: Articles were searched and reviewed from PubMed, research gate, google scholar using the terms BCI, neuroplasticity, motor functions, neurorehabilitation etc. only the studies which were fully accessible; showed positive outcomes; focusing on motor recovery and neuro rehab were included and the studies which focused on other uses of BCI such as gaming, commercial applications and those that focused on measuring non motor functions and cognitive impairments were excluded. Results and Conclusion: After reviewing the articles it was concluded that BCI in combination with conventional rehab techniques and advanced technologies promote neuroplasticity thereby improving functions through repeated activation of neurons and improving coordination and motor function by enhancing the brain connectivity. Implications: The invention of BCI and its combination with other rehab processes aids in the improvement of motor recovery and an overall improvement in ADL’s and quality of life of patients suffering from various neurological disorders.

NEUROBICS: A VITAL ADJUNCT TO PHYSICAL THERAPY IN IMPROVING COGNITIVE AND PHYSICAL FUNCTIONS IN A PREGNANT WOMAN WITH WERNICKE'S ENCEPHALOPATHY - A CASE REPORT.

Background: Wernicke’s Encephalopathy (WE) is a neurological disorder caused by thiamine deficiency, leading to cognitive and physical impairments like confusion, ataxia, and ophthalmoplegia. Pregnant women with WE face additional challenges due to pregnancy demands. This case report examines the use of neurobics—cognitive exercises to stimulate brain function - as an adjunct to physical therapy in enhancing cognitive and physical recovery in a pregnant woman with WE. Objective: This report aims to demonstrate the benefits of combining neurobics with physical therapy to improve cognitive and physical outcomes in a pregnant woman with WE. Case Presentation: A 28-year-old pregnant woman in her second trimester, diagnosed with WE, presented with confusion, ataxia, and visual disturbances. After stabilization with intravenous thiamine, a rehabilitation program combining neurobics and physical therapy was initiated. Physical therapy targeted balance, coordination, and strength, while neurobics engaged the brain with unusual sensory stimuli and non-routine tasks to enhance cognitive function. Results: After four weeks, the patient’s cognitive function improved, with her MoCA score increasing from 4 to 17. Significant gains were seen in executive function, attention, language, visuospatial skills, and orientation, though memory remained unchanged. Ataxia symptoms also improved, with her SARA score reducing from 22 to 14. Conclusion: The integration of neurobics with physical therapy offered a comprehensive approach to rehabilitation in this pregnant woman with WE. Neurobics enhanced cognitive recovery alongside physical rehabilitation, suggesting its potential as a valuable adjunct in managing WE.

Dysgraphia and Memory: Insights into the Cognitive Mechanisms, Neural Correlates, and Intervention Strategies.

Studies regarding dysgraphia, an impairment in writing, have been receiving more attention in recent research. Most studies have broadly discussed the multiple cognitive mechanisms involved in writing and its disruption leading to dysgraphia. However, little attention has been paid to the involvement of different memory systems integral to writing and its disruption in individuals with dysgraphia. Orthographic long-term memory and orthographic working memory are the two memory systems predominantly involved in the production of written expressions, and the subsequent interruption of these memory systems often leads to varied deficit profiles of dysgraphia. These disruptions have resulted from damage in the brain caused by neural injuries, neurological disorders, or epigenetic factors. The existing studies did not probe into the nuances of the disruptions of these two memory systems in dysgraphia and associated neural pathways. In order to fill this gap, the review attempts to provide a comprehensive account of dysgraphia and its association with orthographic long-term memory and orthographic working memory by comparing and contrasting their workings and patterns of disruption in the deficit profiles of dysgraphia by probing into the underlying neural correlates. Such a detailed account brings insights into pertinent intervention strategies for improving memory systems and dysgraphia. It also helps identify the limitations of the existing intervention methods like CART, ACT, or Spell-Study-Spell, leading to the proposal of improvised neuro-targeted interventions for dysgraphia.

Adalimumab induced CNS demyelination in a patient with multiple pre-existing autoimmune diseases; treatment contemplation.

Anti-TNF agents like Adalimumab are safe and effective for rheumatologic disorders, but they have been reported to cause demyelinating diseases like Multiple Sclerosis (MS). A 47-year-old woman with left hand weakness was evaluated. She had a previous medical history of Intermediate Uveitis (IU) and Rheumatoid arthritis (RA). anti-TNF-α treatment was initiated with adalimumab two years before this visit. MRI showed numerous T2-hyperintense lesions in bilateral periventricular, juxtacortical, and subcortical areas, which were absent in her scan before anti-TNF therapy. She was diagnosed with MS, and Adalimumab was discontinued. IV glucocorticoids (GCs) were administered with marked improvement. She was then started on anti-CD20 therapy with Rituximab. A year later, she was symptom-free, and her follow-up Brain MRI showed no new lesions. The link between MS and TNF-α inhibitors is poorly understood, but several hypotheses have been proposed. Discontinuing anti-TNF therapy alone may not be enough to prevent further demyelinating disease activity, and it is essential to consider the necessity of starting a disease-modifying treatment. Autoimmunity plays a significant role in rheumatologic and neurological diseases, and as personalized medicine advances, understanding genetic risk is crucial for selecting appropriate therapeutic targets. A thorough evaluation of a patient's family background is recommended before therapeutic decision-making, especially in patients with multiple autoimmune disorders, and the question of whether TNF-α is a suitable therapeutic target in patients with multiple autoimmune disorders is raised.

Tryptophan-immunoadsorption plasmapheresis regulates polymorphonuclear-myeloid-derived suppressor cells and pro-inflammatory cytokines.

Immunoadsorption plasmapheresis (IA) has been reported to have immunoregulatory effects, in addition to the removal of autoantibodies. This study aimed to investigate the effects of IA on the proportion of myeloid-derived suppressor cells (MDSCs) that potentially suppress autoimmune responses and regulate immunity. The study included 21 patients with autoimmune neurological diseases and 8 healthy participants. We measured polymorphonuclear (PMN)-MDSCs (CD14-CD11b+CD33+) and inflammation-related mediators before and after a single session of tryptophan-IA. We also investigated whether an increase in PMN-MDSCs after initial IA was a predictor of clinical efficacy in nine patients with myasthenia gravis based on the Quantitative Myasthenia Gravis score. For a total of 36 times of IA procedures, the number of PMN-MDSCs significantly increased after IA. Interleukin-10, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1β levels showed significant increases after IA. Despite similar severity at admission, the Quantitative Myasthenia Gravis scores at discharge were significantly lower in the group in which IA increased PMN-MDSCs to a level of 20% of peripheral blood mononuclear cells or more. Tryptophan-IA regulates PMN-MDSCs and pro-inflammatory cytokines, possibly leading to suppression of autoimmune responses and tissue damage in neuroimmunological disorders.

Role of Plant Phytochemicals: Resveratrol, Curcumin, Luteolin and Quercetin Indemyelination, Neurodegeneration, and Epilepsy

Polyphenols are an important group of biologically active compounds present in almost all food sources of plant origin and are primarily known for their anti-inflammatory and antioxidative capabilities. Numerous studies have indicated their broad spectrum of pharmacological properties and correlations between their increased supply in the human diet and lower prevalence of various disorders. The positive effects of polyphenols application are mostly discussed in terms of cardiovascular system well-being. However, in recent years, they have also increasingly mentioned as prophylactic and therapeutic factors in the context of neurological diseases, being able to suppress the progression of such disorders and soothe accompanying symptoms. Among over 8000 various compounds, that have been identified, the most widely examined comprise resveratrol, curcumin, luteolin and quercetin. This review focuses on in vitro assessments, animal models and clinical trials, reflecting the most actual state of knowledge, of mentioned polyphenols’ medicinal capabilities in epilepsy, demyelinating and neurodegenerative diseases of the central nervous system.

Caloric requirement targets for nutritional support in adult autoimmune encephalitis: a retrospective cohort study.

Autoimmune encephalitis (AE) is a severe neurological disease often accompanied by consciousness disturbances, severe swallowing difficulties, and gastrointestinal dysfunction, increasing the risk of malnutrition. However, the optimal caloric intake target during the acute phase of AE remains unclear. This study aims to evaluate the impact of caloric intake on short-term clinical outcomes in AE patients, specifically focusing on the improvement in Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, to provide recommendations for nutritional support during the acute phase. A retrospective study analyzed clinical data from 128 adult AE patients requiring nutritional support, admitted to West China Hospital, Sichuan University, from January 2020 to January 2024. Patients were categorized into low-calorie intake (below 70% of requirements), standard-calorie intake (70-100% of requirements), and high-calorie intake (above 100% of requirements) groups. Multivariate linear and logistic regression models were used to quantify the associations. Higher caloric intake was significantly associated with improved CASE scores (β = 8.58, SE = 3.75, 95% CI = 1.14 to 16.03, p = 0.02). Low caloric intake negatively impacted the improvement of CASE scores (p = 0.049), particularly in seizures and speech problems. The low-calorie intake group had significantly longer hospital stays and nutrition therapy durations (45.79 ± 30.98 days, p < 0.01; 40.39 ± 31.92 days, p = 0.02). Adequate caloric intake has a significant positive impact on the short-term clinical outcomes of AE patients, suggesting that meeting or exceeding caloric requirements may promote neurological recovery in AE patients. Future prospective studies are needed to validate these findings and further optimize nutritional support strategies.

Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects

Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington’s disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.

Erdheim-Chester disease is often complicated by neurological disorders.

Erdheim-Chester disease is often complicated by neurological disorders.

Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.

Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

Accelerated Simulations Reveal Physicochemical Factors Governing Stability and Composition of RNA Clusters.

Under certain conditions, RNA repeat sequences phase separate, yielding protein-free biomolecular condensates. Importantly, RNA repeat sequences have also been implicated in neurological disorders, such as Huntington's disease. Thus, mapping repeat sequences to their phase behavior, functions, and dysfunctions is an active area of research. However, despite several advances, it remains challenging to characterize the RNA phase behavior at a submolecular resolution. Here, we have implemented a residue-resolution coarse-grained model in LAMMPS─that incorporates both the RNA sequence and structure─to study the clustering propensities of protein-free RNA systems. Importantly, we achieve a multifold speedup in the simulation time compared to previous work. Leveraging this efficiency, we study the clustering propensity of all 20 nonredundant trinucleotide repeat sequences. Our results align with findings from experiments, emphasizing that canonical base-pairing and G-U wobble pairs play dominant roles in regulating cluster formation of RNA repeat sequences. Strikingly, we find strong entropic contributions to the stability and composition of RNA clusters, which is demonstrated for single-component RNA systems as well as binary mixtures of trinucleotide repeats. Additionally, we investigate the clustering behaviors of trinucleotide (odd) repeats and their quadranucleotide (even) counterparts. We observe that odd repeats exhibit stronger clustering tendencies, attributed to the presence of consecutive base pairs in their sequences that are disrupted in even repeat sequences. Altogether, our work extends the set of computational tools for probing RNA cluster formation at submolecular resolution and uncovers physicochemical principles that govern the stability and composition of the resulting clusters.

Gut dysbiosis mediates the association between antibiotic exposure and chronic disease

Antibiotics are safe, effective drugs and continue to save millions of lives and prevent long-term illness worldwide. A large body of epidemiological, interventional and experimental evidence shows that exposure to antibiotics has long-term negative effects on human health. We reviewed the literature data on the links between antibiotic exposure, gut dysbiosis, and chronic disease (notably with regard to the “developmental origins of health and disease” (“DOHaD”) approach). Molecular biology studies show that the systemic administration of antibiotic to infants has a rapid onset but also often a long-lasting impact on the microbial composition of the gut. Along with other environmental factors (e.g., an unhealthy “Western” diet and sedentary behavior), antibiotics induce gut dysbiosis, which can be defined as the disruption of a previously stable, functionally complete microbiota. Gut dysbiosis many harmful long-term effects on health. Associations between early-life exposure to antibiotics have been reported for chronic diseases, including inflammatory bowel disease, celiac disease, some cancers, metabolic diseases (obesity and type 2 diabetes), allergic diseases, autoimmune disorders, atherosclerosis, arthritis, and neurodevelopmental, neurodegenerative and other neurological diseases. In mechanistic terms, gut dysbiosis influences chronic disease through direct effects on mucosal immune and inflammatory pathways, plus a wide array of direct or indirect effects of short-chain fatty acids, the enteric nervous system, peristaltic motility, the production of hormones and neurotransmitters, and the loss of intestinal barrier integrity (notably with leakage of the pro-inflammatory endotoxin lipopolysaccharide into the circulation). To mitigate dysbiosis, the administration of probiotics in patients with chronic disease is often (but not always) associated with positive effects on clinical markers (e.g., disease scores) and biomarkers of inflammation and immune activation. Meta-analyses are complicated by differences in probiotic composition, dose level, and treatment duration, and large, randomized, controlled clinical trials are lacking in many disease areas. In view of the critical importance of deciding whether or not to prescribe antibiotics (especially to children), we suggest that the DOHaD concept can be logically extended to “gastrointestinal origins of health and disease” (“GOHaD”) or even “microbiotic origins of health and disease” (“MOHaD”).

YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases.

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.

Single-cell analysis of osmoregulation reveals heterogeneity of aquaporin 4 functionality in human astrocytes.

The water channel aquaporin 4 (AQP4) contributes to water flow and waste removal across the blood-brain barrier and its levels, organization and localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of AQP4 function are performed with primary rodent cells and do not consider inter-cellular variations in AQP4 abundance and presentation. To address this, we have established and applied a robust live cell microscopy assay that captures the contribution of AQP4 in the osmotically driven (de-)quenching of the vital dye Calcein-AM with single-cell resolution. Using human astrocytoma cells, we found that performing measurements on cellular regions instead of whole fields of view yielded a more sensitive readout of the osmotic response, which correlated with AQP4 abundance. Stable co-expression of the two major AQP4 isoforms, but not of the individual isoforms, provoked a faster adaptation to osmotic changes, while siRNA-mediated knockdown of AQP4 had the opposite effect. Post-hoc correlation with the canonical membrane marker CD44 revealed that the speed of the osmotic response scaled with AQP4 membrane enrichment. Coating the substrate with laminin promoted AQP4 membrane enrichment, while cell confinement with fixed-size micropatterns further increased the speed of osmoregulation, underscoring the influence of extracellular factors. The osmotic response of primary fetal astrocytes and human iPSC-derived astrocyte models was comparable to AQP4-deficient astrocytoma cells, in line with their low AQP4 levels and indicative of their immature state. In conclusion, a correlative single-cell approach based on the quantification of Calcein-AM quenching capacity, AQP4 abundance and AQP4 membrane enrichment, allows resolving osmoregulation in a more sensitive manner and reveals heterogeneity between and within human astrocyte (-like) cultures, which could prove crucial for future screens aimed at identifying AQP4 modulators.

Cohort studies on 71 outcomes among people with atopic eczema in UK primary care data.

Atopic eczema may be related to multiple subsequent adverse health outcomes. Here, we provide evidence to judge and compare associations between eczema and a comprehensive set of outcomes. We conducted 71 cohort studies (age, sex, general practice-matched) using Clinical Practice Research Datalink Aurum primary care records (1997-2023), comparing up to 3.6 million people with eczema to 16.8 million without. Eczema was associated with subsequent diagnosis of outcomes with adjusted hazard ratios (99% confidence intervals) from Cox regression of up to 4.02(3.95-4.10) for food allergy (rate difference [RD] per 1,000 person-years of 1.5). Besides strong associations with atopic and allergic conditions (e.g., asthma 1.87[1.39-1.82], RD5.4) and skin infections (e.g., molluscum contagiosum 1.81[1.64-1.96], RD1.8), the strongest associations were with Hodgkin's lymphoma (1.85[1.66-2.06], RD0.02), Alopecia Areata (1.77[1.71-1.83], RD0.2), Crohn's disease (1.62[1.54-1.69], RD0.1), Urticaria (1.58[1.57-1.60], RD1.9), Coeliac disease (1.42[1.37-1.47], RD0.1), Ulcerative colitis (1.40[1.34-1.46], RD0.1), Autoimmune liver disease (1.32[1.21-1.43], RD0.01), and Irritable bowel syndrome (1.31[1.29-1.32], RD0.7). Sensitivity analyses revealed the impact of consultation bias or choice of cohort age cut-off on findings. Comparatively large HRs in severe eczema were seen for some liver, gastrointestinal and cardiovascular conditions, osteoporosis, and fractures. Most cancers and neurological conditions were not associated with eczema.

Comparison of dry and wet electroencephalography for the assessment of cognitive evoked potentials and sensor-level connectivity

BackgroundMultipin dry electrodes (dry EEG) provide faster and more convenient application than wet EEG, enabling extensive data collection. This study aims to compare task-related time-frequency representations and resting-state connectivity between wet and dry EEG methods to establish a foundation for using dry EEG in investigations of brain activity in neuropsychiatric disorders.MethodsIn this counterbalanced cross-over study, we acquired wet and dry EEG in 33 healthy participants [n = 22 females, mean age (SD) = 24.3 (± 3.4) years] during resting-state and an auditory oddball paradigm. We computed mismatch negativity (MMN), theta power in task EEG, and connectivity measures from resting-state EEG using phase lag index (PLI) and minimum spanning tree (MST). Agreement between wet and dry EEG was assessed using Bland–Altman bias.ResultsMMN was detectable with both systems in time and frequency domains, but dry EEG underestimated MMN mean amplitude, peak latency, and theta power compared to wet EEG. Resting-state connectivity was reliably estimated with dry EEG using MST diameter in all except the very low frequencies (0.5–4 Hz). PLI showed larger differences between wet and dry EEG in all frequencies except theta.ConclusionDry EEG reliably detected MMN and resting-state connectivity despite a lower signal-to-noise ratio. This study provides the methodological basis for using dry EEG in studies investigating the neural processes underlying psychiatric and neurological conditions.

Towards Understanding the Role of the Glycosylation of Proteins Present in Extracellular Vesicles in Urinary Tract Diseases: Contributions to Cancer and Beyond

Extracellular vesicles (EVs) are a population of nanoscale particles surrounded by a phospholipid bilayer, enabling intercellular transfer of bioactive molecules. Once released from the parental cell, EVs can be found in most biological fluids in the human body and can be isolated from them. For this reason, EVs have significant diagnostic potential and can serve as an excellent source of circulating disease biomarkers. Protein glycosylation plays a key role in many biological processes, and aberrant glycosylation is a hallmark of various diseases. EVs have been shown to carry multiple glycoproteins, but little is known about the specific biological roles of these glycoproteins in the context of EVs. Moreover, specific changes in EV glycosylation have been described for several diseases, including cancers and metabolic, cardiovascular, neurological or kidney diseases. Urine is the richest source of EVs, providing almost unlimited (in terms of volume) opportunities for non-invasive EV isolation. Recent studies have also revealed a pathological link between urinary EV glycosylation and urological cancers, as well as other pathologies of the urinary tract. In this review, we discuss recent research advances in this field and the diagnostic/prognostic potential of urinary EV glycosylation. In addition, we summarize common methods for isolating EVs from urine and techniques used to study their glycosylation.

The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely play a pivotal role in neurorepair. One way that microglia exert their effects is through the secretion of small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication through transported cargoes of proteins, lipids, RNA, and other bioactive molecules that can alter the behavior of the cells that internalize them. Under normal physiological conditions, MGEVs are essential to homeostasis, whereas the dysregulation of their production and/or alterations in their cargoes have been implicated in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), spinal cord injury (SCI), and traumatic brain injury (TBI). In contrast, MGEVs may also offer therapeutic potential by reversing inflammation or being amenable to engineering for the delivery of beneficial biologics or drugs. The effects of MGEVs are determined by the phenotypic state of the parent microglia. Exosomes from anti-inflammatory or pro-regenerative microglia support neurorepair and cell survival by delivering neurotrophic factors, anti-inflammatory mediators, and molecular chaperones. Further, MGEVs can also deliver components like mitochondrial DNA (mtDNA) and proteins to damaged neurons to enhance cellular metabolism and resilience. MGEVs derived from pro-inflammatory microglia can have detrimental effects on neural health. Their cargo often contains pro-inflammatory cytokines, molecules involved in oxidative stress, and neurotoxic proteins, which can exacerbate neuroinflammation, contribute to neuronal damage, and impair synaptic function, hindering neurorepair processes. The role of MGEVs in neurodegeneration and injury—whether beneficial or harmful—largely depends on how they modulate inflammation through the pro- and anti-inflammatory factors in their cargo, including cytokines and microRNAs. In addition, through the propagation of pathological proteins, such as amyloid-beta and alpha-synuclein, MGEVs can also contribute to disease progression in disorders such as AD and PD, or by the transfer of apoptotic or necrotic factors, they can induce neuron toxicity or trigger glial scarring during neurological injury. In this review, we have provided a comprehensive and up-to-date understanding of the molecular mechanisms underlying the multifaceted role of MGEVs in neurological injury and disease. In particular, the role that specific exosome cargoes play in various pathological conditions, either in disease progression or recovery, will be discussed. The therapeutic potential of MGEVs has been highlighted including potential engineering methodologies that have been employed to alter their cargoes or cell-selective targeting. Understanding the factors that influence the balance between beneficial and detrimental exosome signaling in the CNS is crucial for developing new therapeutic strategies for neurodegenerative diseases and neurotrauma.

Advanced neuroprosthetic electrode design optimized by electromagnetic finite element simulation: innovations and applications

Based on electrophysiological activity, neuroprostheses can effectively monitor and control neural activity. Currently, electrophysiological neuroprostheses are widely utilized in treating neurological disorders, particularly in restoring motor, visual, auditory, and somatosensory functions after nervous system injuries. They also help alleviate inflammation, regulate blood pressure, provide analgesia, and treat conditions such as epilepsy and Alzheimer’s disease, offering significant research, economic, and social value. Enhancing the targeting capabilities of neuroprostheses remains a key objective for researchers. Modeling and simulation techniques facilitate the theoretical analysis of interactions between neuroprostheses and the nervous system, allowing for quantitative assessments of targeting efficiency. Throughout the development of neuroprostheses, these modeling and simulation methods can save time, materials, and labor costs, thereby accelerating the rapid development of highly targeted neuroprostheses. This article introduces the fundamental principles of neuroprosthesis simulation technology and reviews how various simulation techniques assist in the design and performance enhancement of neuroprostheses. Finally, it discusses the limitations of modeling and simulation and outlines future directions for utilizing these approaches to guide neuroprosthesis design.

Synthesizing network pharmacology, bioinformatics, and in vitro experimental verification to screen candidate targets of Salidroside for mitigating Alzheimer's disease.

Alzheimer's disease (AD) is a neurological disorder leading to cognitive deficits. Salidroside (Sal), a primary bioactive ingredient extracted from the roots of Rhodiola rosea L., has potent neuroprotective effects in AD. However, studies on potential targets for Sal-anchored AD are limited. In this study, we combined network pharmacology, bioinformatics, and experimental validation to identify potential targets of Sal treating AD. First, we screened 10 pyroptosis-related genes (PRGs) in Sal and AD using public databases. Then, we used Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis to explore the biological functions of the shared PRGs (Sal and AD). This finding exhibited that pathways linked to inflammation, like the nucleotide oligomerization domain (NOD)-like receptors signaling pathway, are important for Sal to help fight AD. The GeneMANIA functional results subsequently revealed an association between AD and the processes of inflammasome complex and inflammatory response. Additionally, nine hub genes were identified in the protein-protein interaction network of these shared PRGs. Subsequent analysis of the genes and phenotypes confirmed that these nine hub genes were directly correlated with AD. Subsequently, an in vitro AD model was created using rat adrenal pheochromocytoma cell line (PC12) cells induced by amyloid β-peptide (Aβ) 25-35 (20µM). Sal significantly reduced the pyroptosis caused by Aβ 25-35 in PC12 cells and decreased the expression levels of IL-1β, CASP1, IL-18, PYCARD, and NLRP3. Furthermore, molecular docking and molecular dynamics simulations confirmed that Sal could stably bind to NLRP3. Druggability analysis revealed that Sal had excellent druggability. These results demonstrated that Sal could alleviate AD by targeting IL-1β, CASP1, IL-18, PYCARD, and NLRP3 to regulate the NLRP3-mediated pyroptosis signaling pathway.