BACKGROUND Stress hyperglycemia(SH)is a common phenomenon that is present in about 50%of patients with acute ischemic stroke(AIS).It is thought to be a main risk factor for poor functional outcome among patients with ...BACKGROUND Stress hyperglycemia(SH)is a common phenomenon that is present in about 50%of patients with acute ischemic stroke(AIS).It is thought to be a main risk factor for poor functional outcome among patients with AIS undergoing intravenous thrombolysis(IVT).AIM To investigate the predictive value of glycemic indicators for early neurological outcomes(ENOs)in patients with AIS treated with IVT.METHODS We retrospectively reviewed a prospectively collected database of patients with AIS who underwent IVT at the Department of Neurology,Second Affiliated Hospital of Xuzhou Medical University,between January 2017 and June 2022.ENO included early neurological improvement(ENI)and early neurological deterioration(END),defined as a decrease or increase in the National Institutes of Health Stroke Scale(NIHSS)score between baseline and 24 hours after IVT.We analyzed the associations between glycemic indicators[including admission hyperglycemia(AH),fasting blood glucose(FBG),and SH ratio(SHR)]and ENO in all patients and in subgroups stratified by diabetes mellitus(DM).RESULTS A total of 819 patients with AIS treated with IVT were included.Among these,AH was observed in 329 patients(40.2%).Compared with patients without AH,those with AH were more likely to have a higher prevalence of DM(P<0.001)and hypertension(P=0.031)and presented with higher admission NIHSS scores(P<0.001).During the first 24 hours after IVT,END occurred in 208 patients(25.4%)and ENI occurred in 156 patients(19.0%).Multivariate mixed logistic regression analyses indicated that END was independently associated with AH[odds ratio(OR):1.744,95%confidence interval(CI):1.236-2.463;P=0.002].Subjects were classified into four groups representing quartiles.Compared with Q1,patients in the higher quartiles of SHR(Q2:OR:2.306,95%CI:1.342-3.960;P=0.002)(Q3:OR:2.284,95%CI:1.346-3.876;P=0.002)(Q4:OR:3.486,95%CI:2.088-5.820;P=0.001)and FBG(Q3:OR:1.746,95%CI:1.045-2.917;P=0.033)(Q4:OR:2.436,95%CI:1.476-4.022;P=0.001)had a significantly higher risk of END in the overall population.However,none of the glycemic indicators were found to be associated with ENI in patients with or without DM.CONCLUSION Our study demonstrated that glycemic indicators in patients with stroke treated with IVT were associated with the presence of END rather than ENI during the first 24 hours after admission.展开更多
Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National In...Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.展开更多
The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central n...The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.展开更多
Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–b...Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.展开更多
BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pe...BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pediatric populations remains under-researched,with challenges in diagnosis and management AIM To synthesize the current literature on FND in children,focusing on clinical presentation,diagnostic approaches,treatment strategies,and outcomes.METHODS A comprehensive literature search was conducted across multiple databases,including PubMed,Scopus,and Web of Science,for articles published up to August 2024.Studies were included if they addressed FND in pediatric populations,specifically focusing on review articles,research articles,systematic reviews,meta-analyses,case reports,guidelines,expert opinions,and editorials.Data extraction and quality assessment were performed according to PRISMA guidelines.A total of 308 articles were included in the final analysis.RESULTS The analysis included 189 review articles,57 research articles,3 systematic reviews and meta-analyses,5 case reports,2 guidelines,5 expert opinions,and 2 editorials.Key findings revealed a broad spectrum of symptoms,including motor and sensory disturbances and psychological factors contributing to the onset and persistence of FND.Diagnostic challenges were frequently highlighted,emphasizing the need for interdisciplinary approaches.Treatment strategies varied,with cognitive-behavioral therapy(CBT)and multidisciplinary care emerging as the most effective approaches.The outcomes varied,with early intervention being critical for a better prognosis.CONCLUSION Early diagnosis and multidisciplinary care,including CBT,are critical for improving outcomes in pediatric FND.Standardized diagnostic criteria and treatment protocols are needed to enhance clinical management.展开更多
Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological d...Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.展开更多
With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely o...With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.展开更多
Objective:To evaluate the predictive value of Modified Early Warning Score(MEWS)for neurological disease prognosis and identify prognostic factors.Methods:This retrospective study analyzed 768 neurological patients wi...Objective:To evaluate the predictive value of Modified Early Warning Score(MEWS)for neurological disease prognosis and identify prognostic factors.Methods:This retrospective study analyzed 768 neurological patients with MEWS≥4(June 2022–June 2024).Patients were stratified by outcomes(favorable/unfavorable).Multivariable logistic regression and ROC analysis were performed.Results:108 cases(13.1%)had unfavorable outcomes.Significant prognostic factors included:age,TBI history,onset-to-admission time,PT,MEWS score,and MEWS≥4 frequency(all P<0.05).MEWS showed AUC=0.749(sensitivity 62.0%,specificity 77.4%).Conclusion:MEWS demonstrates moderate predictive value(AUC=0.749)for neurological outcomes.Consciousness assessment limitations(56.5%impaired cases)may affect sensitivity.A specialized model incorporating pupillary reflexes and GCS is recommended for improved early warning.展开更多
BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose ...BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose conditions more quickly and effectively,ultimately benefiting patients.AIM To explore the current status and key highlights of AI-related articles in diagnosing of neurological disorders.METHODS A systematic literature review was conducted in the Web of Science Core Collection database using the following strategy:TS=("Artificial Intelligence"OR"Computational Intelligence"OR"Machine Learning"OR"AI")AND TS=("Neurological disorders"OR"CNS disorder"AND"diagnosis").The search was limited to articles and reviews.Microsoft Excel 2019 and VOSviewer were utilized to identify major contributors,including authors,institutions,countries,and journals.Additionally,VOSviewer was employed to analyze and visualize current trends and hot topics through network visualization maps.RESULTS A total of 276 publications from 2000 to 2024 were retrieved.The United States,India,and China emerged as the top contributors in this field.Major institutions included Johns Hopkins University,King's College London,and Harvard Medical School.The most prolific author was U.Rajendra Acharya from the University of Southern Queensland(Australia).Among journals,IEEE Access,Scientific Reports,and Sensors were the most productive,while Frontiers in Neuroscience led in total citations.Central topics in AI-related articles on neurological disorders diagnosis included Alzheimer's disease,Parkinson's disease,dementia,epilepsy,autism,attention deficit hyperactivity disorder,and their intersections with deep learning and AI.CONCLUSION Research on AI's role in diagnosing neurological disorders is becoming widely recognized for its growing importance.AI shows promise in diagnosing various neurological disorders,yet requires further improvement and extensive future research.展开更多
BACKGROUND Pancreas transplantation(PT)has emerged as a critical therapeutic intervention for patients with type 1 diabetes mellitus(T1DM).This procedure restores neuroendocrine communication,which is essential for op...BACKGROUND Pancreas transplantation(PT)has emerged as a critical therapeutic intervention for patients with type 1 diabetes mellitus(T1DM).This procedure restores neuroendocrine communication,which is essential for optimal pancreatic function and insulin regulation.The recovery process involves multiple phases,including neural regeneration,revascularization,and the re-establishment of synaptic connections,all of which contribute to the restoration of both endocrine and neurological functions.AIM To systematically examine the mechanisms underlying neurological recovery following PT,to explore the role of endocrine factors in restoring neurofunctional integrity,and to evaluate the impact of immunosuppressive therapy on nerve regeneration and its clinical outcomes.METHODS A comprehensive literature search was conducted across international databases such as PubMed,Web of Science,and Cochrane Library to identify studies addressing PT,neurological recovery,and endocrine regulation.Inclusion criteria encompassed randomized controlled trials,cohort studies,and systematic reviews.The review focused on the neurogenic mechanisms activated post-transplantation,the effect of glycemic control on nerve repair,and the implications of immunosuppressive drugs on the process of neurological recovery.RESULTS A total of 211 articles were initially identified through the literature search across international databases such as PubMed,Web of Science,and Cochrane Library.Following a detailed evaluation and the application of inclusion and exclusion criteria,56 articles were further reviewed,and 8 were selected for the final analysis.Additionally,a comprehensive patent search yielded 168 patents,out of which 6 were selected for further examination.These sources,including both journal literature and patents,offer significant insights into the mechanisms of neurological recovery and endocrine function following PT,with an emphasis on nerve regeneration,glycemic control,and the impact of immunosuppressive therapy.CONCLUSION PT represents a promising intervention for restoring both endocrine and neurological functions in patients with T1DM.Glycemic control,neural regeneration,and the restoration of neuroendocrine signaling are key components of successful recovery.While the procedure yields substantial improvements in nerve function,challenges persist,particularly in patients with long-standing diabetes or severe neuropathy.The dual impact of immunosuppressive drugs on immune suppression and neurotoxicity necessitates careful management.Future research should focus on refining immunosuppressive protocols and exploring advanced therapeutic options,including stem cell-based interventions,to enhance neural regeneration and further improve clinical outcomes.展开更多
Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can con...Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.展开更多
BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognost...BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognostic value for 28-day neurological outcomes.METHODS:In this prospective observational cohort study,plasma iron metabolism-related parameters(iron,ferritin,hepcidin,soluble transferrin receptor[sTfR],total iron binding capacity[TIBC],and transferrin saturation),interleukin-6,and neuron-specific enolase(NSE)were assessed in 120 patients after restoration of spontaneous circulation(ROSC)on days 1 and 3 of intensive care unit(ICU)admission and in 40 healthy controls.The primary outcome was poor 28-day neurological prognosis.RESULTS:Compared to controls,post-ROSC patients exhibited significant plasma iron metabolism disturbances,including decreased iron,TIBC,transferrin saturation,with elevated hepcidin,ferritin,sTfR,interleukin-6,and NSE on day 1 after ICU admission(P<0.05 for all).On day 28 post-ROSC,patients with poor neurological outcomes(71/120)presented more pronounced alterations than those with good neurological outcomes.Binary logistic analysis revealed that a plasma iron concentration≤11.2μmol/L(odds ratio[OR]0.607,95% confidence interval[CI]0.455-0.808)and an NSE concentration≥20.5 ng/mL(OR 1.020,95%CI 1.005-1.035)on day 1 of ICU admission were associated with 28-day poor neurological outcomes.The plasma iron-NSE combination showed better predictive performance(area under the curve=0.935,sensitivity 89.8%,specificity 84.5%).CONCLUSION:Early post-ROSC plasma iron metabolism disturbances combined with NSE elevation were associated with the 28-day neurological prognosis,suggesting the therapeutic potential of targeting the iron metabolism pathway.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
Objective:To analyze the clinical application and effects of the body restraint reduction program for severe neurological patients.Methods:A total of 206 patients admitted to the neurology department of the hospital f...Objective:To analyze the clinical application and effects of the body restraint reduction program for severe neurological patients.Methods:A total of 206 patients admitted to the neurology department of the hospital from January 2022 to May 2025 were selected as the research subjects.Among them,102 patients from January 2022 to May 2025 were assigned to the observation group,and 104 patients during the same period served as the control group.In practice,the control group received conventional body restraint,while the observation group adopted the reduction program.The incidence of unplanned extubation and restraint-related complications were compared between the two groups.Results:The body restraint rate and complication rate in the observation group were significantly lower(P<0.05).After nurse training,their knowledge mastery and operational ability were significantly higher than before training(P<0.01).Conclusion:The body restraint reduction program for severe neurological patients can effectively reduce the restraint rate and complication incidence,while helping improve nurses’restraint management capabilities,serving as an effective means to enhance overall nursing quality.展开更多
Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,...Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently elucidated.In this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory microenvironment.Conversely,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after SCI.UTX forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional repair.Furthermore,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after SCI.In conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.展开更多
Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple pro...Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.展开更多
Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimer...Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo.In chimeric brains,human neural and immune cells can maintain human-specific features,undergo maturation,and functionally integrate into host brains,allowing scientists to study how human cells impact neural circuits and animal behaviors.The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease,elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels,and testing the efficacy of cell therapy interventions.Here,we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders,including disease modeling and cell therapy.展开更多
Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perf...Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.展开更多
Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highes...Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highest levels of metabolic complexity,have developed an elegant system that uses constant and rechargeable energy sources of modulate their metabolism.This homeostasis is especially important in the central nervous system,as neurons and other cells in the brain are highly susceptible to fluctuations in nutrients and oxygen availability.展开更多
基金Supported by the Foundation of Jiangsu Provincial Commission of Health and Family Planning,No.QNRC2016353the Commission of Health and Family Planning Xuzhou,No.KC22206.
文摘BACKGROUND Stress hyperglycemia(SH)is a common phenomenon that is present in about 50%of patients with acute ischemic stroke(AIS).It is thought to be a main risk factor for poor functional outcome among patients with AIS undergoing intravenous thrombolysis(IVT).AIM To investigate the predictive value of glycemic indicators for early neurological outcomes(ENOs)in patients with AIS treated with IVT.METHODS We retrospectively reviewed a prospectively collected database of patients with AIS who underwent IVT at the Department of Neurology,Second Affiliated Hospital of Xuzhou Medical University,between January 2017 and June 2022.ENO included early neurological improvement(ENI)and early neurological deterioration(END),defined as a decrease or increase in the National Institutes of Health Stroke Scale(NIHSS)score between baseline and 24 hours after IVT.We analyzed the associations between glycemic indicators[including admission hyperglycemia(AH),fasting blood glucose(FBG),and SH ratio(SHR)]and ENO in all patients and in subgroups stratified by diabetes mellitus(DM).RESULTS A total of 819 patients with AIS treated with IVT were included.Among these,AH was observed in 329 patients(40.2%).Compared with patients without AH,those with AH were more likely to have a higher prevalence of DM(P<0.001)and hypertension(P=0.031)and presented with higher admission NIHSS scores(P<0.001).During the first 24 hours after IVT,END occurred in 208 patients(25.4%)and ENI occurred in 156 patients(19.0%).Multivariate mixed logistic regression analyses indicated that END was independently associated with AH[odds ratio(OR):1.744,95%confidence interval(CI):1.236-2.463;P=0.002].Subjects were classified into four groups representing quartiles.Compared with Q1,patients in the higher quartiles of SHR(Q2:OR:2.306,95%CI:1.342-3.960;P=0.002)(Q3:OR:2.284,95%CI:1.346-3.876;P=0.002)(Q4:OR:3.486,95%CI:2.088-5.820;P=0.001)and FBG(Q3:OR:1.746,95%CI:1.045-2.917;P=0.033)(Q4:OR:2.436,95%CI:1.476-4.022;P=0.001)had a significantly higher risk of END in the overall population.However,none of the glycemic indicators were found to be associated with ENI in patients with or without DM.CONCLUSION Our study demonstrated that glycemic indicators in patients with stroke treated with IVT were associated with the presence of END rather than ENI during the first 24 hours after admission.
文摘Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
基金supported by the National Natural Science Foundation of China,Nos.81901098(to TC),82201668(to HL)Fujian Provincial Health Technology Project,No.2021QNA072(to HL)。
文摘The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.
基金supported by the National Natural Science Foundation of China,Nos.82171363,82371381(to PL),82171458(to XJ)Key Research and Development Project of Shaa nxi Province,Nos.2024SF-YBXM-404(to KY)。
文摘Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.
文摘BACKGROUND Functional neurological disorder(FND)in children is a complex and multifaceted condition characterized by neurological symptoms that cannot be explained by organic pathology.Despite its prevalence,FND in pediatric populations remains under-researched,with challenges in diagnosis and management AIM To synthesize the current literature on FND in children,focusing on clinical presentation,diagnostic approaches,treatment strategies,and outcomes.METHODS A comprehensive literature search was conducted across multiple databases,including PubMed,Scopus,and Web of Science,for articles published up to August 2024.Studies were included if they addressed FND in pediatric populations,specifically focusing on review articles,research articles,systematic reviews,meta-analyses,case reports,guidelines,expert opinions,and editorials.Data extraction and quality assessment were performed according to PRISMA guidelines.A total of 308 articles were included in the final analysis.RESULTS The analysis included 189 review articles,57 research articles,3 systematic reviews and meta-analyses,5 case reports,2 guidelines,5 expert opinions,and 2 editorials.Key findings revealed a broad spectrum of symptoms,including motor and sensory disturbances and psychological factors contributing to the onset and persistence of FND.Diagnostic challenges were frequently highlighted,emphasizing the need for interdisciplinary approaches.Treatment strategies varied,with cognitive-behavioral therapy(CBT)and multidisciplinary care emerging as the most effective approaches.The outcomes varied,with early intervention being critical for a better prognosis.CONCLUSION Early diagnosis and multidisciplinary care,including CBT,are critical for improving outcomes in pediatric FND.Standardized diagnostic criteria and treatment protocols are needed to enhance clinical management.
基金supported by AFM-Telethon grants N°21704 and 23264,Universite Paris Cite(Paris)the National Institute of Health and Medical Research(INSERM)+3 种基金the National Center for Scientific Research(CNRS)the French Association Connaître les Syndromes Cerebelleux(CSC)(to MCD)GV/2021/188 granted from Conselleria of Innovation,Universities,28 Science and Society digital of the Community of Valencia(Spain)(to ITC)Subprograma Atraccion de Talento-Contratos Postdoctorales de la Universitat de Valencia(to IMY).
文摘Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.
文摘With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.
基金Research on the Measurement of Pulmonary Compliance and Its Guided Therapeutic Efficacy Analysis in Patients with ARDS Secondary to Severe Multiple Injuries(Project No.:XSD2023002)。
文摘Objective:To evaluate the predictive value of Modified Early Warning Score(MEWS)for neurological disease prognosis and identify prognostic factors.Methods:This retrospective study analyzed 768 neurological patients with MEWS≥4(June 2022–June 2024).Patients were stratified by outcomes(favorable/unfavorable).Multivariable logistic regression and ROC analysis were performed.Results:108 cases(13.1%)had unfavorable outcomes.Significant prognostic factors included:age,TBI history,onset-to-admission time,PT,MEWS score,and MEWS≥4 frequency(all P<0.05).MEWS showed AUC=0.749(sensitivity 62.0%,specificity 77.4%).Conclusion:MEWS demonstrates moderate predictive value(AUC=0.749)for neurological outcomes.Consciousness assessment limitations(56.5%impaired cases)may affect sensitivity.A specialized model incorporating pupillary reflexes and GCS is recommended for improved early warning.
文摘BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose conditions more quickly and effectively,ultimately benefiting patients.AIM To explore the current status and key highlights of AI-related articles in diagnosing of neurological disorders.METHODS A systematic literature review was conducted in the Web of Science Core Collection database using the following strategy:TS=("Artificial Intelligence"OR"Computational Intelligence"OR"Machine Learning"OR"AI")AND TS=("Neurological disorders"OR"CNS disorder"AND"diagnosis").The search was limited to articles and reviews.Microsoft Excel 2019 and VOSviewer were utilized to identify major contributors,including authors,institutions,countries,and journals.Additionally,VOSviewer was employed to analyze and visualize current trends and hot topics through network visualization maps.RESULTS A total of 276 publications from 2000 to 2024 were retrieved.The United States,India,and China emerged as the top contributors in this field.Major institutions included Johns Hopkins University,King's College London,and Harvard Medical School.The most prolific author was U.Rajendra Acharya from the University of Southern Queensland(Australia).Among journals,IEEE Access,Scientific Reports,and Sensors were the most productive,while Frontiers in Neuroscience led in total citations.Central topics in AI-related articles on neurological disorders diagnosis included Alzheimer's disease,Parkinson's disease,dementia,epilepsy,autism,attention deficit hyperactivity disorder,and their intersections with deep learning and AI.CONCLUSION Research on AI's role in diagnosing neurological disorders is becoming widely recognized for its growing importance.AI shows promise in diagnosing various neurological disorders,yet requires further improvement and extensive future research.
基金Supported by National Natural Science Foundation of China,No.82305376The Project of Supporting Young Scientific and Technological Talents in Jiangsu Province in 2024,No.JSTJ-2024-380.
文摘BACKGROUND Pancreas transplantation(PT)has emerged as a critical therapeutic intervention for patients with type 1 diabetes mellitus(T1DM).This procedure restores neuroendocrine communication,which is essential for optimal pancreatic function and insulin regulation.The recovery process involves multiple phases,including neural regeneration,revascularization,and the re-establishment of synaptic connections,all of which contribute to the restoration of both endocrine and neurological functions.AIM To systematically examine the mechanisms underlying neurological recovery following PT,to explore the role of endocrine factors in restoring neurofunctional integrity,and to evaluate the impact of immunosuppressive therapy on nerve regeneration and its clinical outcomes.METHODS A comprehensive literature search was conducted across international databases such as PubMed,Web of Science,and Cochrane Library to identify studies addressing PT,neurological recovery,and endocrine regulation.Inclusion criteria encompassed randomized controlled trials,cohort studies,and systematic reviews.The review focused on the neurogenic mechanisms activated post-transplantation,the effect of glycemic control on nerve repair,and the implications of immunosuppressive drugs on the process of neurological recovery.RESULTS A total of 211 articles were initially identified through the literature search across international databases such as PubMed,Web of Science,and Cochrane Library.Following a detailed evaluation and the application of inclusion and exclusion criteria,56 articles were further reviewed,and 8 were selected for the final analysis.Additionally,a comprehensive patent search yielded 168 patents,out of which 6 were selected for further examination.These sources,including both journal literature and patents,offer significant insights into the mechanisms of neurological recovery and endocrine function following PT,with an emphasis on nerve regeneration,glycemic control,and the impact of immunosuppressive therapy.CONCLUSION PT represents a promising intervention for restoring both endocrine and neurological functions in patients with T1DM.Glycemic control,neural regeneration,and the restoration of neuroendocrine signaling are key components of successful recovery.While the procedure yields substantial improvements in nerve function,challenges persist,particularly in patients with long-standing diabetes or severe neuropathy.The dual impact of immunosuppressive drugs on immune suppression and neurotoxicity necessitates careful management.Future research should focus on refining immunosuppressive protocols and exploring advanced therapeutic options,including stem cell-based interventions,to enhance neural regeneration and further improve clinical outcomes.
基金supported by the 2024 Talent Project of Shandong First Medical University(045RC200008)the Taishan Scholars Program(tsqn202211225).
文摘Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(SZXK046)the Shenzhen Science and Technology Program(JCYJ20230807112007014).
文摘BACKGROUND:Iron metabolism dyshomeostasis is associated with ferroptosis and ischemiareperfusion injury.We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognostic value for 28-day neurological outcomes.METHODS:In this prospective observational cohort study,plasma iron metabolism-related parameters(iron,ferritin,hepcidin,soluble transferrin receptor[sTfR],total iron binding capacity[TIBC],and transferrin saturation),interleukin-6,and neuron-specific enolase(NSE)were assessed in 120 patients after restoration of spontaneous circulation(ROSC)on days 1 and 3 of intensive care unit(ICU)admission and in 40 healthy controls.The primary outcome was poor 28-day neurological prognosis.RESULTS:Compared to controls,post-ROSC patients exhibited significant plasma iron metabolism disturbances,including decreased iron,TIBC,transferrin saturation,with elevated hepcidin,ferritin,sTfR,interleukin-6,and NSE on day 1 after ICU admission(P<0.05 for all).On day 28 post-ROSC,patients with poor neurological outcomes(71/120)presented more pronounced alterations than those with good neurological outcomes.Binary logistic analysis revealed that a plasma iron concentration≤11.2μmol/L(odds ratio[OR]0.607,95% confidence interval[CI]0.455-0.808)and an NSE concentration≥20.5 ng/mL(OR 1.020,95%CI 1.005-1.035)on day 1 of ICU admission were associated with 28-day poor neurological outcomes.The plasma iron-NSE combination showed better predictive performance(area under the curve=0.935,sensitivity 89.8%,specificity 84.5%).CONCLUSION:Early post-ROSC plasma iron metabolism disturbances combined with NSE elevation were associated with the 28-day neurological prognosis,suggesting the therapeutic potential of targeting the iron metabolism pathway.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
文摘Objective:To analyze the clinical application and effects of the body restraint reduction program for severe neurological patients.Methods:A total of 206 patients admitted to the neurology department of the hospital from January 2022 to May 2025 were selected as the research subjects.Among them,102 patients from January 2022 to May 2025 were assigned to the observation group,and 104 patients during the same period served as the control group.In practice,the control group received conventional body restraint,while the observation group adopted the reduction program.The incidence of unplanned extubation and restraint-related complications were compared between the two groups.Results:The body restraint rate and complication rate in the observation group were significantly lower(P<0.05).After nurse training,their knowledge mastery and operational ability were significantly higher than before training(P<0.01).Conclusion:The body restraint reduction program for severe neurological patients can effectively reduce the restraint rate and complication incidence,while helping improve nurses’restraint management capabilities,serving as an effective means to enhance overall nursing quality.
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金funded by National Natural Science Foundation of China(grant 82030071 and 82272495)Natural Science Foundation of Hunan Province(grant 2020JJ5930 and 2020JJ4874)the Science and Technology Major Project of Changsha(No.kh2103008).
文摘Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently elucidated.In this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory microenvironment.Conversely,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after SCI.UTX forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional repair.Furthermore,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after SCI.In conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.
基金supported by the National Natural Science Foundation of China(Nos.32000692 and 32200816).
文摘Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.
文摘Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo.In chimeric brains,human neural and immune cells can maintain human-specific features,undergo maturation,and functionally integrate into host brains,allowing scientists to study how human cells impact neural circuits and animal behaviors.The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease,elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels,and testing the efficacy of cell therapy interventions.Here,we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders,including disease modeling and cell therapy.
文摘Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.
基金RTDC postdoctoral fellowship is defrayed by an AHA Supplement to Promote Diversity in Science.MES is funded by AHA(Career Development Award),Rutgers University(StartUp Funds),and NIH(R00AG055701).
文摘Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highest levels of metabolic complexity,have developed an elegant system that uses constant and rechargeable energy sources of modulate their metabolism.This homeostasis is especially important in the central nervous system,as neurons and other cells in the brain are highly susceptible to fluctuations in nutrients and oxygen availability.
