Introduction: Pain has been defined for more than 20 years by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue dam...Introduction: Pain has been defined for more than 20 years by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. It has been recognized as a feature of Parkinson’s disease (PD) since the first descriptions of the disease. Material and Methods: This was a prospective descriptive study lasting six (06) months from November 1, 2023 to April 30, 2024. We included all patients diagnosed with PD and who had pain. Sociodemographic, clinical, paraclinical and therapeutic data were evaluated for each patient. Results: We identified a sample of 62 Parkinson’s patients, of whom 52 patients or 85.2% had associated pain. We noted a male predominance (38M/14F) and a sex ratio of 2.71. Musculoskeletal pain was common in 80% of our respondents. WHO level I, antidepressants and background treatment for KD were the most prescribed molecules. Conclusion: Our study shows a frequency of pain in PD. However, musculoskeletal pain is the most frequently encountered type of pain in PD patients. WHO step I analgesics, antidepressants and background treatment of KD were the main prescriptions in our study.展开更多
Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions th...Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.展开更多
Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increa...Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.展开更多
Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from cli...Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.展开更多
Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbl...Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).展开更多
Background:Recently,there has been a surge in research worldwide on vitamin D.based on international level,Vit.D has shown positive correlation with cardio-cerebrovascular disorders.Regarding possible role of vitamin ...Background:Recently,there has been a surge in research worldwide on vitamin D.based on international level,Vit.D has shown positive correlation with cardio-cerebrovascular disorders.Regarding possible role of vitamin D there is paucity of research in low-and middle-income nations that are nearer to the equatorial area.Despite of abundant sunlight exposure,Asian people are developing hypovitaminosis D need a special consideration to avoid excessive and unnecessary usage of it.This study aims to detect the situation of vitamin D in Nepalese population and secondly to find out the suitable normalized reference range for serum vitamin D in multi-ethnic Nepalese population.Methods:A hospital based prospective study was conducted using purposive sampling technique to select 107 subjects.In-vivo and in vitro bio-physiological method was used to collect serum vitamin D level.Result:The present study showed that 32%of participants had deficit(<15 ng/mL),48%of subjects had insufficient(15 to<30 ng/mL)and 20%of participants had sufficient serum level of Vitamin-D(>30 ng/mL).Study showed that there is a lower degree of positive relationship of body mass index(r=0.162,P=0.094)and significant association of history of chronic illness(χ2=0.10,P=0.03),timing of occurrence of stroke(χ2=11.41,P=0.017)and diagnosis(χ2=21.19,P=0.011)with serum vitamin-D level at P<0.05.Conclusion:There is a direct significant association of serum vitamin D with socio-demographic variables when international unit is considered.Neurological disorder showed positive association with serum vitamin D level.展开更多
Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host def...Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult（removing offending factors）and restoring structure and function of the brain（establish homeostasis）.The timing of these protective functions of the immune response is vital,since chronic inflammation展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and...Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart disease.In that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.展开更多
Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy i...Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy in the short-term treatment of various cognitive impairments.This study evaluated the efficacy of butylphthalide in preventing cognitive decline over a 12-month period in patients with ischaemic stroke.Methods This prospective following-up study involved patients newly diagnosed with ischaemic stroke between 1 month and 6 months after stroke onset and not in the acute phase.Patients were assigned to either the butylphthalide or control group.Cognitive function was assessed using the mini-mental state examination(MMSE)at baseline and at the 12-month follow-up.Statistical analyses included t-tests,χ2 tests and multivariate regression analyses.Results Butylphthalide was negatively associated with the MMSE D-value(β=−0.122;95%CI−1.932 to−0.298;p=0.003)and the MMSE D-value percentage(β=−0.117;95%CI−0.057 to−0.011;p=0.004).A multivariate analysis indicated that butylphthalide treatment was negatively associated with both changes in orientation and language score.Additionally,the incidence of cognitive decline was significantly lower in the butylphthalide group(OR,0.612;p=0.020)than the control group.An age of≥60 years and lower educational level were identified as risk factors for lower cognitive score and cognitive decline.Conclusion This study demonstrated that butylphthalide is effective in preventing cognitive decline in patients with ischaemic stroke.These findings have significant implications for clinical practice,suggesting that butylphthalide could be incorporated into standard post-stroke care regimens to improve patient outcomes and reduce the healthcare burden.Additional multicentre double-blind trials are recommended to confirm these results in diverse populations.展开更多
Background:Subcortical ischemic vascular dementia(SIVD)is a common subtype of vascular dementia.Currently,the bilateral common carotid artery stenosis(BCAS)mouse model is the most suitable SIVD rodent model.In this st...Background:Subcortical ischemic vascular dementia(SIVD)is a common subtype of vascular dementia.Currently,the bilateral common carotid artery stenosis(BCAS)mouse model is the most suitable SIVD rodent model.In this study,we investigated the functional and structural impairments in the hippocampus 1 month after BCAS.Methods:We used behavioral tests,laser speckle flowmetry,long-term potentiation,histochemical staining,molecular experiments,and voxel-based morphometry to evaluate the hippocampal impairments.Results:Behavioral studies revealed that BCAS mice exhibited worse performance.Laser speckle flowmetry detected an obvious decrease in cerebral blood flow.The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited.Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data.A reduction in gray matter volume,which was most prominent in the hippocampus and its surrounding areas,was de-tected via voxel-based morphometry analysis.Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques.In addition,the numbers of GFAP+astrocytes and Iba1+microglia in-creased in the hippocampus.Conclusions:Overall,our study demonstrates early functional and structural impair-ments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS,indicating that the hippocampus is vulnerable to chronic cerebral ischemia.展开更多
Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammal...Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammalian cortical radial glial cells(primary neural stem cells)and introduces the concept that a genetically step wise process,based on a core molecular pathway already in use,is the evolutionary process that has molded cortical neurogenesis.The core mechanism,which has been identified in our recent studies,is the extracellular signal-regulated kinase(ERK)-bone morphogenic protein 7(BMP7)-GLI3 repressor form(GLI3R)-sonic hedgehog(SHH)positive feedback loop.Additionally,I propose that the molecular basis for cortical evolutionary dwarfism,exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor,is an increase in SHH signaling in radial glia,that antagonizes ERK-BMP7 signaling.Finally,I propose that:(1)SHH signaling is not a key regulator of primate cortical expansion and folding;(2)human cortical radial glial cells do not generate neocortical interneurons;(3)human-specific genes may not be essential for most cortical expansion.I hope this review assists colleagues in the field,guiding research to address gaps in our understanding of cortical development and evolution.展开更多
With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative ...With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative disease of neurodegenerative diseases,has become a major challenge,affecting the health and quality of life of the elderly population severely.In recent years,the incidence,prevalence and mortality rates of AD have increased in China,imposing substantial economic burdens on families,society and the entire healthcare system.To proactively address this challenge and respond to the national‘Healthy China Action’initiative,leading experts from authoritative institutions jointly authored the China Alzheimer Report 2025.Building on previous editions,this report updates epidemiological data on AD in China,thoroughly analyses the latest economic burdens of the disease and comprehensively evaluates the current status of AD diagnosis and treatment services,as well as the allocation of public health resources in our country.Its release reflects China’s progress in AD research and prevention,underscores societal concern for elderly health and aims to provide scientific guidance and data support for AD prevention,diagnosis and treatment.It also facilitates academic exchanges and cooperation,enhancing public awareness and promoting active participation in elderly healthcare,towards achieving‘healthy ageing’in China.展开更多
Ultrasound-enabled nanomedicine leverages ultrasound to amplify the capabilities of engineered nanosystems,paving the way for innovative diagnostic and therapeutic breakthroughs in conventional nanomedicine.As a burge...Ultrasound-enabled nanomedicine leverages ultrasound to amplify the capabilities of engineered nanosystems,paving the way for innovative diagnostic and therapeutic breakthroughs in conventional nanomedicine.As a burgeoning discipline,past overviews have sometimes offered a fragmented perspective,lacking a comprehensive view.This review presents a systematic exploration of the latest advancements in ultrasound-enabled nanomedicine,with a particular emphasis on oncology.Covered topics include molecular imaging of tumors,separation of tumor markers,penetration through physiological barriers,perforation of cell membranes,targeted drug release and activation strategies,and an array of sonotherapies for oncological treatments.We delve into the research framework of each topic,the foundational design of the nanosystems,and their associated ultrasound activation mechanisms.Moreover,we highlight recent pivotal research aimed at deepening the reader’s understanding of this intricate domain.This review underscores the integration of design and foundational theories within ultrasound-enabled nanomedicine,aspiring to ignite advanced theoretical insights and introduce innovative design paradigms.In conclusion,we outline current challenges and prospective research directions.An enhanced focus on these areas will expedite the advancement of ultrasound-enabled nanomedicine.展开更多
Background Social media listening is a new approach for gathering insights from social media platforms about users experiences.This approach has not been applied to analyse discussions about Alzheimer's disease(AD...Background Social media listening is a new approach for gathering insights from social media platforms about users experiences.This approach has not been applied to analyse discussions about Alzheimer's disease(AD)in China.Aims We aimed to leverage multisource Chinese data to gain deeper insights into the current state of the daily management of Chinese patients with AD and the burdens faced by their caregivers.Methods We searched ninemainstreampublic onlineplatforms in China fromSeptember2010 to March 2024.Natural language processing tools were used to identify patients and caregivers,and categorise patients by disease stage forfurther analysis.We analysed the current state of patient daily management,including diagnosis and treatment,choice oftreatment scenarios,patient safetyand caregiverconcerns.Results Atotal of 1211patientswithAD(66% female,82% aged 60-90)and 756caregiversfor patients with AD were identified from 107556 online sources.Most patients were derived from online consultation platforms(43%),followed by bulletin board system platforms(24%).Among the patients categorised into specific disease stages(n=382),42% were in the moderate stage.The most frequent diagnostic tools included medical history(97%)and symptoms(84%).Treatment options for patients with AD primarily included cholinesterase inhibitors,N-methyl-D-aspartate receptor antagonists and antipsychotics.Both quantitative and qualitative analysis of patients whoexperiencedwandering(n=92)indicated a higher incidence of wandering during the moderate stage of the disease.Most caregivers were family members,with their primary concerns focusing on disease management and treatment(90%),followed by daily life care(37%)and psychosocial support(25%).Conclusions Online platform data provide a broad spectrum of real-world insights into individuals affected byAD in China.This study enhances our understanding of the experiences of patients with AD and their caregivers,providing guidance for developing personalised interventions,providing advicefor caregivers and improving care for patients with AD.展开更多
The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions...The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions,but its role in early brain injury(EBI)after SAH remains unclear.In this study,we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms.WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue,correlating negatively with microglial activation.AAV-WNK1 alleviated brain edema,neuronal necrosis,behavioral deficits,and inflammation by inhibiting NLRP3 inflammasome activation.In hemin-stimulated BV-2 cells,WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines.Chloride counteracted WNK1’s inhibitory effects,and WNK1 suppressed P2X7R-induced NLRP3 activation.Mechanistically,WNK1 functioned via the OXSR1/STK39 pathway.These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation,presenting a potential therapeutic target for SAH treatment.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
Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous famil...Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous family with biallelic variants in MED16 identified by exome sequencing.The affected individuals present with global developmental delay,intellectual disability,and dysmorphisms.To assess the pathogenicity of the variants,functional studies are performed in Drosophila and patient-derived cells.The fly ortholog med16 is expressed in neurons and some glia of the developing central nervous system(CNS).Loss of med16 leads to a reduction in eclosion and lifespan,as well as impaired synaptic transmission.In neurons differentiated from the patient-derived induced pluripotent stem cells(iPSCs),the neurite outgrowth is impaired and rescued by expression of exogenous MED16.The patient-associated variants behave as loss-of-function(LoF)alleles in flies and iPSCs.Additionally,the transcription of genes related to neuronal maturation and function is preferentially altered in patient cells relative to differentiated H9 controls.In summary,our findings support that MED16 is important for appropriate development and function,and that biallelic MED16 variants cause a neurodevelopmental disease.展开更多
文摘Introduction: Pain has been defined for more than 20 years by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. It has been recognized as a feature of Parkinson’s disease (PD) since the first descriptions of the disease. Material and Methods: This was a prospective descriptive study lasting six (06) months from November 1, 2023 to April 30, 2024. We included all patients diagnosed with PD and who had pain. Sociodemographic, clinical, paraclinical and therapeutic data were evaluated for each patient. Results: We identified a sample of 62 Parkinson’s patients, of whom 52 patients or 85.2% had associated pain. We noted a male predominance (38M/14F) and a sex ratio of 2.71. Musculoskeletal pain was common in 80% of our respondents. WHO level I, antidepressants and background treatment for KD were the most prescribed molecules. Conclusion: Our study shows a frequency of pain in PD. However, musculoskeletal pain is the most frequently encountered type of pain in PD patients. WHO step I analgesics, antidepressants and background treatment of KD were the main prescriptions in our study.
基金support held by JPA,Collaborative Network Award BRAVEinMS,Grant/Award Number:PA-1604-08492(MG)from the Multiple Sclerosis Society of Canada,Grant/Award Number:1038154(to TEK).
文摘Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.
基金supported by the National Natural Science Foundation of China(82271401,82071394)the Tianjin Health Research Project(TJWJ2024RC002)。
文摘Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111123(to JQ)。
文摘Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
基金supported by China Scholarship Council(No.202106380078 to HL)the Netherlands Cardiovascular Research Initiative:The Dutch Heart Foundation(CVON 2018-28 and 2012-06 Heart Brain Connection to AMT)。
文摘Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).
文摘Background:Recently,there has been a surge in research worldwide on vitamin D.based on international level,Vit.D has shown positive correlation with cardio-cerebrovascular disorders.Regarding possible role of vitamin D there is paucity of research in low-and middle-income nations that are nearer to the equatorial area.Despite of abundant sunlight exposure,Asian people are developing hypovitaminosis D need a special consideration to avoid excessive and unnecessary usage of it.This study aims to detect the situation of vitamin D in Nepalese population and secondly to find out the suitable normalized reference range for serum vitamin D in multi-ethnic Nepalese population.Methods:A hospital based prospective study was conducted using purposive sampling technique to select 107 subjects.In-vivo and in vitro bio-physiological method was used to collect serum vitamin D level.Result:The present study showed that 32%of participants had deficit(<15 ng/mL),48%of subjects had insufficient(15 to<30 ng/mL)and 20%of participants had sufficient serum level of Vitamin-D(>30 ng/mL).Study showed that there is a lower degree of positive relationship of body mass index(r=0.162,P=0.094)and significant association of history of chronic illness(χ2=0.10,P=0.03),timing of occurrence of stroke(χ2=11.41,P=0.017)and diagnosis(χ2=21.19,P=0.011)with serum vitamin-D level at P<0.05.Conclusion:There is a direct significant association of serum vitamin D with socio-demographic variables when international unit is considered.Neurological disorder showed positive association with serum vitamin D level.
文摘Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult（removing offending factors）and restoring structure and function of the brain（establish homeostasis）.The timing of these protective functions of the immune response is vital,since chronic inflammation
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金supported by JSPS KAKENHI Grant Number JP24K18622(to TI)JSPS KAKENHI Grant Number JP23K18451(to TM)。
文摘Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart disease.In that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.
基金funded by Tianjin Municipal Health Commission(TJWJ2023QN115)。
文摘Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy in the short-term treatment of various cognitive impairments.This study evaluated the efficacy of butylphthalide in preventing cognitive decline over a 12-month period in patients with ischaemic stroke.Methods This prospective following-up study involved patients newly diagnosed with ischaemic stroke between 1 month and 6 months after stroke onset and not in the acute phase.Patients were assigned to either the butylphthalide or control group.Cognitive function was assessed using the mini-mental state examination(MMSE)at baseline and at the 12-month follow-up.Statistical analyses included t-tests,χ2 tests and multivariate regression analyses.Results Butylphthalide was negatively associated with the MMSE D-value(β=−0.122;95%CI−1.932 to−0.298;p=0.003)and the MMSE D-value percentage(β=−0.117;95%CI−0.057 to−0.011;p=0.004).A multivariate analysis indicated that butylphthalide treatment was negatively associated with both changes in orientation and language score.Additionally,the incidence of cognitive decline was significantly lower in the butylphthalide group(OR,0.612;p=0.020)than the control group.An age of≥60 years and lower educational level were identified as risk factors for lower cognitive score and cognitive decline.Conclusion This study demonstrated that butylphthalide is effective in preventing cognitive decline in patients with ischaemic stroke.These findings have significant implications for clinical practice,suggesting that butylphthalide could be incorporated into standard post-stroke care regimens to improve patient outcomes and reduce the healthcare burden.Additional multicentre double-blind trials are recommended to confirm these results in diverse populations.
基金supported by Tianjin Key Medical Discipline(Specialty)Construction Project(grant number TJYXZDXK-004A).
文摘Background:Subcortical ischemic vascular dementia(SIVD)is a common subtype of vascular dementia.Currently,the bilateral common carotid artery stenosis(BCAS)mouse model is the most suitable SIVD rodent model.In this study,we investigated the functional and structural impairments in the hippocampus 1 month after BCAS.Methods:We used behavioral tests,laser speckle flowmetry,long-term potentiation,histochemical staining,molecular experiments,and voxel-based morphometry to evaluate the hippocampal impairments.Results:Behavioral studies revealed that BCAS mice exhibited worse performance.Laser speckle flowmetry detected an obvious decrease in cerebral blood flow.The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited.Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data.A reduction in gray matter volume,which was most prominent in the hippocampus and its surrounding areas,was de-tected via voxel-based morphometry analysis.Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques.In addition,the numbers of GFAP+astrocytes and Iba1+microglia in-creased in the hippocampus.Conclusions:Overall,our study demonstrates early functional and structural impair-ments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS,indicating that the hippocampus is vulnerable to chronic cerebral ischemia.
基金supported by the Ministry of Science and Technology of China(STI2030-2021ZD0202300)the National Natural Science Foundation of China(32070971,32100768,32200776,and 32200792)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammalian cortical radial glial cells(primary neural stem cells)and introduces the concept that a genetically step wise process,based on a core molecular pathway already in use,is the evolutionary process that has molded cortical neurogenesis.The core mechanism,which has been identified in our recent studies,is the extracellular signal-regulated kinase(ERK)-bone morphogenic protein 7(BMP7)-GLI3 repressor form(GLI3R)-sonic hedgehog(SHH)positive feedback loop.Additionally,I propose that the molecular basis for cortical evolutionary dwarfism,exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor,is an increase in SHH signaling in radial glia,that antagonizes ERK-BMP7 signaling.Finally,I propose that:(1)SHH signaling is not a key regulator of primate cortical expansion and folding;(2)human cortical radial glial cells do not generate neocortical interneurons;(3)human-specific genes may not be essential for most cortical expansion.I hope this review assists colleagues in the field,guiding research to address gaps in our understanding of cortical development and evolution.
基金supported by a grant from Brain Science and BrainLike Intelligence Technology of the Ministry of Science and Technology of China(2021ZD0201804).
文摘With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative disease of neurodegenerative diseases,has become a major challenge,affecting the health and quality of life of the elderly population severely.In recent years,the incidence,prevalence and mortality rates of AD have increased in China,imposing substantial economic burdens on families,society and the entire healthcare system.To proactively address this challenge and respond to the national‘Healthy China Action’initiative,leading experts from authoritative institutions jointly authored the China Alzheimer Report 2025.Building on previous editions,this report updates epidemiological data on AD in China,thoroughly analyses the latest economic burdens of the disease and comprehensively evaluates the current status of AD diagnosis and treatment services,as well as the allocation of public health resources in our country.Its release reflects China’s progress in AD research and prevention,underscores societal concern for elderly health and aims to provide scientific guidance and data support for AD prevention,diagnosis and treatment.It also facilitates academic exchanges and cooperation,enhancing public awareness and promoting active participation in elderly healthcare,towards achieving‘healthy ageing’in China.
基金financially supported by the National Natural Science Foundation of China(32271440)the Tianjin Health Research Project(TJWJ2023ZD001).
文摘Ultrasound-enabled nanomedicine leverages ultrasound to amplify the capabilities of engineered nanosystems,paving the way for innovative diagnostic and therapeutic breakthroughs in conventional nanomedicine.As a burgeoning discipline,past overviews have sometimes offered a fragmented perspective,lacking a comprehensive view.This review presents a systematic exploration of the latest advancements in ultrasound-enabled nanomedicine,with a particular emphasis on oncology.Covered topics include molecular imaging of tumors,separation of tumor markers,penetration through physiological barriers,perforation of cell membranes,targeted drug release and activation strategies,and an array of sonotherapies for oncological treatments.We delve into the research framework of each topic,the foundational design of the nanosystems,and their associated ultrasound activation mechanisms.Moreover,we highlight recent pivotal research aimed at deepening the reader’s understanding of this intricate domain.This review underscores the integration of design and foundational theories within ultrasound-enabled nanomedicine,aspiring to ignite advanced theoretical insights and introduce innovative design paradigms.In conclusion,we outline current challenges and prospective research directions.An enhanced focus on these areas will expedite the advancement of ultrasound-enabled nanomedicine.
基金funded by the Ministry of Science and Technology of the People's Republic of China(2021ZD0201804,GW).
文摘Background Social media listening is a new approach for gathering insights from social media platforms about users experiences.This approach has not been applied to analyse discussions about Alzheimer's disease(AD)in China.Aims We aimed to leverage multisource Chinese data to gain deeper insights into the current state of the daily management of Chinese patients with AD and the burdens faced by their caregivers.Methods We searched ninemainstreampublic onlineplatforms in China fromSeptember2010 to March 2024.Natural language processing tools were used to identify patients and caregivers,and categorise patients by disease stage forfurther analysis.We analysed the current state of patient daily management,including diagnosis and treatment,choice oftreatment scenarios,patient safetyand caregiverconcerns.Results Atotal of 1211patientswithAD(66% female,82% aged 60-90)and 756caregiversfor patients with AD were identified from 107556 online sources.Most patients were derived from online consultation platforms(43%),followed by bulletin board system platforms(24%).Among the patients categorised into specific disease stages(n=382),42% were in the moderate stage.The most frequent diagnostic tools included medical history(97%)and symptoms(84%).Treatment options for patients with AD primarily included cholinesterase inhibitors,N-methyl-D-aspartate receptor antagonists and antipsychotics.Both quantitative and qualitative analysis of patients whoexperiencedwandering(n=92)indicated a higher incidence of wandering during the moderate stage of the disease.Most caregivers were family members,with their primary concerns focusing on disease management and treatment(90%),followed by daily life care(37%)and psychosocial support(25%).Conclusions Online platform data provide a broad spectrum of real-world insights into individuals affected byAD in China.This study enhances our understanding of the experiences of patients with AD and their caregivers,providing guidance for developing personalised interventions,providing advicefor caregivers and improving care for patients with AD.
基金supported by Grants from the Basic Research Program of Jiangsu(BK20240492)Lianyungang Science and Technology Plan Project(JCYJ2304)+2 种基金Lianyungang Aging Health Research Project(L202301)Doctoral Research Start-up Fund of the First Peopel’Hospital of Lianyungang City(BS202314)The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage(SAH).WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions,but its role in early brain injury(EBI)after SAH remains unclear.In this study,we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms.WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue,correlating negatively with microglial activation.AAV-WNK1 alleviated brain edema,neuronal necrosis,behavioral deficits,and inflammation by inhibiting NLRP3 inflammasome activation.In hemin-stimulated BV-2 cells,WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines.Chloride counteracted WNK1’s inhibitory effects,and WNK1 suppressed P2X7R-induced NLRP3 activation.Mechanistically,WNK1 functioned via the OXSR1/STK39 pathway.These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation,presenting a potential therapeutic target for SAH treatment.
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 the National Key R&D Program of China (2020YFA0112500 and 2021YFA1100400)the National Natural Science Foundation of China (32271019 and 12411530079)+6 种基金the Natural Science Foundation of Shanghai Municipality (22ZR1462600)supported by the Natural Science Foundation of Hunan Province, China (2022JJ40206)Ruixin project of Hunan Provincial Maternal and Child Health Care Hospital (2023RX01)supported by the Clinical Research Center Projects for Genetic Birth Defects and Rare Diseases in Hunan Province (2023SK4053)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1010)supported by the Model Organisms Screening Center of the UDN by U54NS093793 of the NIH (NINDS)supported by the Office of Research Infrastructure Programs of the NIH (awards R24 OD022005 and R24 OD031447).
文摘Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous family with biallelic variants in MED16 identified by exome sequencing.The affected individuals present with global developmental delay,intellectual disability,and dysmorphisms.To assess the pathogenicity of the variants,functional studies are performed in Drosophila and patient-derived cells.The fly ortholog med16 is expressed in neurons and some glia of the developing central nervous system(CNS).Loss of med16 leads to a reduction in eclosion and lifespan,as well as impaired synaptic transmission.In neurons differentiated from the patient-derived induced pluripotent stem cells(iPSCs),the neurite outgrowth is impaired and rescued by expression of exogenous MED16.The patient-associated variants behave as loss-of-function(LoF)alleles in flies and iPSCs.Additionally,the transcription of genes related to neuronal maturation and function is preferentially altered in patient cells relative to differentiated H9 controls.In summary,our findings support that MED16 is important for appropriate development and function,and that biallelic MED16 variants cause a neurodevelopmental disease.
