Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal ...Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.展开更多
Objective:This study aims to explore the facilitating and hindering factors faced by rehabilitation professionals in providing cognitive rehabilitation services for patients with Post-Stroke Cognitive Impairment(PSCI)...Objective:This study aims to explore the facilitating and hindering factors faced by rehabilitation professionals in providing cognitive rehabilitation services for patients with Post-Stroke Cognitive Impairment(PSCI)in China,offering empirical evidence for optimizing service models.Methods:Using purposive sampling,semi-structured interviews were conducted with 15 rehabilitation professionals from three tertiary hospitals and two community health service centers in Hubei Province from September to November 2023.Audio recordings were transcribed to obtain textual data,which were analyzed using Nvivo 12 software for coding.An inductive thematic analysis approach was employed to distill key themes.Results:The study identified multiple facilitating and hindering factors related to cognitive rehabilitation,summarizing them into four core themes and eight sub-themes:(1)Cognitive Screening:Presence of practical barriers and inadequate professional knowledge,which limited early detection and effective intervention for cognitive impairments;(2)Individualized Rehabilitation:Lack of patient-directed personalized interventions and multidisciplinary team collaboration,affecting patient engagement and rehabilitation outcomes;(3)Lack of Psychological Rehabilitation:The necessity of psychological interventions was emphasized,yet there is a significant scarcity of neuropsychological resources,limiting the implementation of psychological support;(4)Challenges of Community Continuity in Rehabilitation:Severe service discontinuity,with community healthcare institutions facing shortages of professional knowledge and equipment,resulting in patients being unable to receive continuous and effective rehabilitation support after discharge.Conclusion:Current PSCI rehabilitation services face issues such as insufficient staffing,ineffective multidisciplinary team collaboration,and a lack of community resources.Enhancing neuropsychological resources,establishing standardized MDT collaboration processes,and creating a referral system linking hospitals,communities,and families are essential to improve primary care capacity and enhance rehabilitation outcomes for patients.展开更多
BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adve...BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adverse effects.Herbal medicine containing Paeoniae Radix(HCP)has traditionally been used in Korean medicine to treat RLS symptoms.AIM To investigate the clinical effectiveness and safety of HCP in treating RLS.METHODS This retrospective chart review study included 15 patients with RLS who were treated with HCP between September 2017 and August 2022 at the Kyung Hee University Korean Medicine Hospital.The demographic,disease-related,and treatment-related characteristics,as well as the impressions of each patient,were analyzed.The study also evaluated the changes in the subjective complaints of RLS symptoms,the Korean version of the International Restless Legs Scale(KIRLS)scores before and after treatment,and the adverse events after HCP administration.RESULTS Following HCP administration,14 patients(93.3%)experienced a decrease in the degree of discomfort associated with their symptoms,with an average reduction to 44.7±35.1%compared to their discomfort levels before taking the drug.After treatment,the mean total K-IRLS score decreased significantly from 23.00±9.75 to 13.93±10.9(P=0.005).Among the HCP,a significant reduction in the K-IRLS score was observed in the Gyejibokryeonghwan(26.0±9.7 to 10.0±9.4,P=0.028)and Jakyakgamchotang(23.2±12.6 to 6.6±4.2,P=0.042)groups.Additionally,no adverse events were reported.CONCLUSION HCP improved symptoms in RLS patients.These results suggest that HCP may be an effective and safe alternative for RLS.A randomized controlled trial is required to confirm these findings.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging.However,investigations into the microstructural pathology of brain white matter(WM)associated with...Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging.However,investigations into the microstructural pathology of brain white matter(WM)associated with these deficits remain limited.This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination,utilizing Neurite Orientation Dispersion and Density Imaging(NODDI),and to explore their correlations with cognitive functions and cognition-related plasma biomarkers.The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls,characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index.Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation,superior longitudinal fasciculus,cingulum,and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers.These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction,potentially serving as early markers for cognitive decline.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechan...Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.展开更多
Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the...Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.展开更多
Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI i...Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.展开更多
OBJECTIVE:To summarize the evidence from Traditional Chinese Medicine(TCM)practice in the treatment of acute primary headache and provide clinical practice guidance.METHODS:The guidelines were developed in accordance ...OBJECTIVE:To summarize the evidence from Traditional Chinese Medicine(TCM)practice in the treatment of acute primary headache and provide clinical practice guidance.METHODS:The guidelines were developed in accordance with the World Health Organization guideline development manual.After the establishment of steering committee,panel and the registration and protocol formulation,the evidence on TCM for acute primary headache from published guidelines,clinical evidence,and expert experience and consensus were collected.The grading of recommendations assessment,development and evaluation method was used to grade the evidence and make the recommendations.RESULTS:Based on the available evidence,the guidelines recommended three TCM herbal decoctions,six Chinese patent medicines,and two kinds of external application of Chinese herbal medicines.Diagnostic recommendations based on the expert experience and consensus were also included in the guidelines.CONCLUSION:TCM diagnosis and treatment of decoction,Chinese patent medicine and external application for treating acute primary headache were recommended.We hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.展开更多
Genetic factors may be learnt from families with gene mutations that render nerve-injury sus- ceptibility even to ordinary physical activities. A typical example is hereditary neuropathy with liability to pressure pal...Genetic factors may be learnt from families with gene mutations that render nerve-injury sus- ceptibility even to ordinary physical activities. A typical example is hereditary neuropathy with liability to pressure palsies （HNPP）. HNPP is caused by a heterozygous deletion of PMP22 gene. PMP22 deficiency disrupts myelin junctions （such as tight junction and adherens junctions）, leading to abnormally increased myelin permeability that explains the nerve susceptibility to injury. This finding should motivate investigators to identify additional genetic factors contribut- ing to nerve vulnerability of injury.展开更多
In 1906,Dr.Alois Alzheimer reported a case of dementia and thought it was a new type of disease.Later,Dr.Emil Kraepelin named it Alzheimer’s disease(AD).One hundred years later,AD has become the most common type of d...In 1906,Dr.Alois Alzheimer reported a case of dementia and thought it was a new type of disease.Later,Dr.Emil Kraepelin named it Alzheimer’s disease(AD).One hundred years later,AD has become the most common type of dementia affecting the elderly population and a heavy health burden.However,the pathogenesis of the disease remains unclear,and no disease-modifying therapies are available to prevent,halt,or even slow the progression of the disease[1].展开更多
Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive,abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potent...Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive,abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potential(TRP) channels, which transduce noxious stimuli into pain signals, are expressed in trigeminal ganglion neurons and brain regions closely associated with the pathophysiology of migraine. In the trigeminal ganglion,TRP channels co-localize with calcitonin gene-related peptide, a neuropeptide crucially implicated in migraine pathophysiology. Many preclinical and clinical data support the roles of TRP channels in migraine. In particular,activation of TRP cation channel V1 has been shown to regulate calcitonin gene-related peptide release from trigeminal nerves. Intriguingly, several effective antimigraine therapies, including botulinum neurotoxin type A, affect the functions of TRP cation channels. Here, we discuss currently available data regarding the roles of major TRP cation channels in the pathophysiology of migraine and the therapeutic applicability thereof.展开更多
The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this ene...The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function.展开更多
More than 2 million new ischemic stroke patients are diagnosed every year in China,with a prevalence of about11 million.Stroke is the leading cause of death in the country[1,2].The therapeutic effect on ischemic strok...More than 2 million new ischemic stroke patients are diagnosed every year in China,with a prevalence of about11 million.Stroke is the leading cause of death in the country[1,2].The therapeutic effect on ischemic stroke in the ultra-early period depends on the timely restoration of the blood supply to rescue brain tissue.展开更多
Insomnia is one of the most frequently observed sleep disorders, affecting nearly 10% of the general population. It has multiple etiological factors. Recently, it has been reported that EEG abnormalities are associate...Insomnia is one of the most frequently observed sleep disorders, affecting nearly 10% of the general population. It has multiple etiological factors. Recently, it has been reported that EEG abnormalities are associated with insomnia in patients previously diagnosed as idiopathic insomniacs. In addition, transcranial magnetic stimulation (TMS) has shown to be effective in the treatment of disorders characterized by neural hyper-excitability. Method: In the present study, patients with insomnia and EEG abnormalities were submitted to slow repetitive trans-cranial magnetic stimulation, for 15 minutes daily during 10 days. Polysomnographic recordings were performed before and after TMS. Results: The results indicate that the presence of EEG abnormalities significantly decreased after TMS. In addition, most of the sleep parameters showed significant improvement. Conclusions: These data support the notion that TMS is a reliable therapeutic tool for patients affected with abnormalities linked to neuronal hyper-excitability.展开更多
Multiple cellular components, including neuronal, glial and endothelial ceils, are involved in the sophis- ticated pathological processes following central nervous system injury. The pathological process cannot reduce...Multiple cellular components, including neuronal, glial and endothelial ceils, are involved in the sophis- ticated pathological processes following central nervous system injury. The pathological process cannot reduce damage or improve functional recovery by merely targeting the molecular mechanisms of neuronal cell death after central nerve system injuries. Eph receptors and ephrin ligands have drawn wide attention since the discovery of their extensive distribution and unique bidirectional signaling between astrocytes and neurons. The roles of Eph/ephrin bidirectional signaling in the developmental processes have been re- ported in previous research. Recent observations suggest that Eph/ephrin bidirectional signaling continues to be expressed in most regions and cell types in the adult central nervous system, playing diverse roles. The Eph/ephrin complex mediates neurogenesis and angiogenesis, promotes glial scar formation, regulates endocrine levels, inhibits myelin formation and aggravates inflammation and nerve pain caused by injury. ~lhe interaction between Eph and ephrin is also considered to be the key to angiogenesis. This review focus- es on the roles of Eph/ephrin bidirectional signaling in the repair of central nervous system injuries.展开更多
With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseas...With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseases (1)Aimed at scientific research and education, the roles of human brain tissue repositories are to acquire brain tissue from donors, prepare, process, and preserve collected samples,provide tissue to specific eligible facilities, and determine the characteristics of each tissue sample.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81920108017(to YX),82130036(to YX),82371326(to XC),82171310(to XC)the STI2030-Major Projects,No.2022ZD0211800(to YX)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)。
文摘Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.
基金Ethics Committee of Taihe Hospital in Shiyan City(Project No.:2023XM008)。
文摘Objective:This study aims to explore the facilitating and hindering factors faced by rehabilitation professionals in providing cognitive rehabilitation services for patients with Post-Stroke Cognitive Impairment(PSCI)in China,offering empirical evidence for optimizing service models.Methods:Using purposive sampling,semi-structured interviews were conducted with 15 rehabilitation professionals from three tertiary hospitals and two community health service centers in Hubei Province from September to November 2023.Audio recordings were transcribed to obtain textual data,which were analyzed using Nvivo 12 software for coding.An inductive thematic analysis approach was employed to distill key themes.Results:The study identified multiple facilitating and hindering factors related to cognitive rehabilitation,summarizing them into four core themes and eight sub-themes:(1)Cognitive Screening:Presence of practical barriers and inadequate professional knowledge,which limited early detection and effective intervention for cognitive impairments;(2)Individualized Rehabilitation:Lack of patient-directed personalized interventions and multidisciplinary team collaboration,affecting patient engagement and rehabilitation outcomes;(3)Lack of Psychological Rehabilitation:The necessity of psychological interventions was emphasized,yet there is a significant scarcity of neuropsychological resources,limiting the implementation of psychological support;(4)Challenges of Community Continuity in Rehabilitation:Severe service discontinuity,with community healthcare institutions facing shortages of professional knowledge and equipment,resulting in patients being unable to receive continuous and effective rehabilitation support after discharge.Conclusion:Current PSCI rehabilitation services face issues such as insufficient staffing,ineffective multidisciplinary team collaboration,and a lack of community resources.Enhancing neuropsychological resources,establishing standardized MDT collaboration processes,and creating a referral system linking hospitals,communities,and families are essential to improve primary care capacity and enhance rehabilitation outcomes for patients.
基金Supported by Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health and Welfare,Republic of Korea,No.RS-2023-KH142002.
文摘BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adverse effects.Herbal medicine containing Paeoniae Radix(HCP)has traditionally been used in Korean medicine to treat RLS symptoms.AIM To investigate the clinical effectiveness and safety of HCP in treating RLS.METHODS This retrospective chart review study included 15 patients with RLS who were treated with HCP between September 2017 and August 2022 at the Kyung Hee University Korean Medicine Hospital.The demographic,disease-related,and treatment-related characteristics,as well as the impressions of each patient,were analyzed.The study also evaluated the changes in the subjective complaints of RLS symptoms,the Korean version of the International Restless Legs Scale(KIRLS)scores before and after treatment,and the adverse events after HCP administration.RESULTS Following HCP administration,14 patients(93.3%)experienced a decrease in the degree of discomfort associated with their symptoms,with an average reduction to 44.7±35.1%compared to their discomfort levels before taking the drug.After treatment,the mean total K-IRLS score decreased significantly from 23.00±9.75 to 13.93±10.9(P=0.005).Among the HCP,a significant reduction in the K-IRLS score was observed in the Gyejibokryeonghwan(26.0±9.7 to 10.0±9.4,P=0.028)and Jakyakgamchotang(23.2±12.6 to 6.6±4.2,P=0.042)groups.Additionally,no adverse events were reported.CONCLUSION HCP improved symptoms in RLS patients.These results suggest that HCP may be an effective and safe alternative for RLS.A randomized controlled trial is required to confirm these findings.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金supported by the Joint Funds for Innovation of Science and Technology,Fujian Province(2021Y9037)a National Clinical Key Special Subject of China(21281003).
文摘Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging.However,investigations into the microstructural pathology of brain white matter(WM)associated with these deficits remain limited.This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination,utilizing Neurite Orientation Dispersion and Density Imaging(NODDI),and to explore their correlations with cognitive functions and cognition-related plasma biomarkers.The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls,characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index.Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation,superior longitudinal fasciculus,cingulum,and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers.These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction,potentially serving as early markers for cognitive decline.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金supported by the National Natural Science Foundation of China(82271334,82130036,81920108017,82171310)the National Science and Technology Innovation 2030--Major Program of"Brain Science and Brain-Like Research"(2022ZD0211800)+1 种基金Jiangsu Provincial‘333’High-level Talent Training Project Funding,the Key Research and Development Program of Jiangsu Province of China(BE2020620)Jiangsu Province Key Medical Discipline(ZDXK202216).
文摘Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.
基金supported by the National Natural Science Foundation of China(81901142)funds for key support objects of Third Military Medical University.
文摘Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
基金supported by the National Natural Science Foundation of China(82071362,82002899)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ202205303001577,JCYJ20190809165201646)Basic Research Projects of Shenzhen Science and Technology Program(JCYJ20180307150610733).
文摘Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.
基金National Key Research and Development Program of China:Research on the Development and Evaluation of International Standards of Traditional Chinese Medicine(No.2019YFC1712000)。
文摘OBJECTIVE:To summarize the evidence from Traditional Chinese Medicine(TCM)practice in the treatment of acute primary headache and provide clinical practice guidance.METHODS:The guidelines were developed in accordance with the World Health Organization guideline development manual.After the establishment of steering committee,panel and the registration and protocol formulation,the evidence on TCM for acute primary headache from published guidelines,clinical evidence,and expert experience and consensus were collected.The grading of recommendations assessment,development and evaluation method was used to grade the evidence and make the recommendations.RESULTS:Based on the available evidence,the guidelines recommended three TCM herbal decoctions,six Chinese patent medicines,and two kinds of external application of Chinese herbal medicines.Diagnostic recommendations based on the expert experience and consensus were also included in the guidelines.CONCLUSION:TCM diagnosis and treatment of decoction,Chinese patent medicine and external application for treating acute primary headache were recommended.We hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.
基金supported by grants from NINDS R01NS066927Department of Veterans Affairs R&D funds
文摘Genetic factors may be learnt from families with gene mutations that render nerve-injury sus- ceptibility even to ordinary physical activities. A typical example is hereditary neuropathy with liability to pressure palsies （HNPP）. HNPP is caused by a heterozygous deletion of PMP22 gene. PMP22 deficiency disrupts myelin junctions （such as tight junction and adherens junctions）, leading to abnormally increased myelin permeability that explains the nerve susceptibility to injury. This finding should motivate investigators to identify additional genetic factors contribut- ing to nerve vulnerability of injury.
基金supported by the National Natural Science Foundation of China(91749206 and 81625007).
文摘In 1906,Dr.Alois Alzheimer reported a case of dementia and thought it was a new type of disease.Later,Dr.Emil Kraepelin named it Alzheimer’s disease(AD).One hundred years later,AD has become the most common type of dementia affecting the elderly population and a heavy health burden.However,the pathogenesis of the disease remains unclear,and no disease-modifying therapies are available to prevent,halt,or even slow the progression of the disease[1].
基金supported by the Japan Society for the Promotion of Science KAKENHI(26460706 and 19K07849)a Japan-China Sasakawa Medical Fellowship(2017816)a State Scholarship Fund of the China Scholarship Council(201908500072)。
文摘Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive,abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potential(TRP) channels, which transduce noxious stimuli into pain signals, are expressed in trigeminal ganglion neurons and brain regions closely associated with the pathophysiology of migraine. In the trigeminal ganglion,TRP channels co-localize with calcitonin gene-related peptide, a neuropeptide crucially implicated in migraine pathophysiology. Many preclinical and clinical data support the roles of TRP channels in migraine. In particular,activation of TRP cation channel V1 has been shown to regulate calcitonin gene-related peptide release from trigeminal nerves. Intriguingly, several effective antimigraine therapies, including botulinum neurotoxin type A, affect the functions of TRP cation channels. Here, we discuss currently available data regarding the roles of major TRP cation channels in the pathophysiology of migraine and the therapeutic applicability thereof.
基金supported in part by National Institutes of Health Grants NS-091201(to MY)and NS-079331(to MY)VA MERIT Award IO1BX003441(to MY)
文摘The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function.
基金the Clinical Medical Research Expert Training Program of Daping Hospital,China(2018XLC2022)。
文摘More than 2 million new ischemic stroke patients are diagnosed every year in China,with a prevalence of about11 million.Stroke is the leading cause of death in the country[1,2].The therapeutic effect on ischemic stroke in the ultra-early period depends on the timely restoration of the blood supply to rescue brain tissue.
文摘Insomnia is one of the most frequently observed sleep disorders, affecting nearly 10% of the general population. It has multiple etiological factors. Recently, it has been reported that EEG abnormalities are associated with insomnia in patients previously diagnosed as idiopathic insomniacs. In addition, transcranial magnetic stimulation (TMS) has shown to be effective in the treatment of disorders characterized by neural hyper-excitability. Method: In the present study, patients with insomnia and EEG abnormalities were submitted to slow repetitive trans-cranial magnetic stimulation, for 15 minutes daily during 10 days. Polysomnographic recordings were performed before and after TMS. Results: The results indicate that the presence of EEG abnormalities significantly decreased after TMS. In addition, most of the sleep parameters showed significant improvement. Conclusions: These data support the notion that TMS is a reliable therapeutic tool for patients affected with abnormalities linked to neuronal hyper-excitability.
基金supported by the National Natural Science Foundation of China,No.81371312,81030021the National Basic Research Development Program of China(973 Program),No.2011CB504403
文摘Multiple cellular components, including neuronal, glial and endothelial ceils, are involved in the sophis- ticated pathological processes following central nervous system injury. The pathological process cannot reduce damage or improve functional recovery by merely targeting the molecular mechanisms of neuronal cell death after central nerve system injuries. Eph receptors and ephrin ligands have drawn wide attention since the discovery of their extensive distribution and unique bidirectional signaling between astrocytes and neurons. The roles of Eph/ephrin bidirectional signaling in the developmental processes have been re- ported in previous research. Recent observations suggest that Eph/ephrin bidirectional signaling continues to be expressed in most regions and cell types in the adult central nervous system, playing diverse roles. The Eph/ephrin complex mediates neurogenesis and angiogenesis, promotes glial scar formation, regulates endocrine levels, inhibits myelin formation and aggravates inflammation and nerve pain caused by injury. ~lhe interaction between Eph and ephrin is also considered to be the key to angiogenesis. This review focus- es on the roles of Eph/ephrin bidirectional signaling in the repair of central nervous system injuries.
文摘With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseases (1)Aimed at scientific research and education, the roles of human brain tissue repositories are to acquire brain tissue from donors, prepare, process, and preserve collected samples,provide tissue to specific eligible facilities, and determine the characteristics of each tissue sample.
