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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu Jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy Anthony Patrizz Li Qi Akihiko Urayama Jun Li department of neurology University of Texas Health Science Center department of neurology&Psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

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Statistical evaluation of cluster formation of relapse in neuromyelitis optica spectrum disorder

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Neural Regeneration Research 2024年第9期19卷 1888-1889页

作者： Tetsuya Akaishi Ichiro Nakashima department of neurology Tohoku UniversitySendaiJapan department of neurology Tohoku Medical and Pharmaceutical UniversitySendaiJapan

Evaluating the cluster formation of clinical attacks in chronic relapsing diseases is an important statistical issue because the presence of attack clusters may influence therapeutic strategies for relapse prevention.We recently reported the occurrence of unevenly clustered attacks in patients with anti-aquaporin-4(AQP4)antibody-positive neuromyelitis optica spectrum disorder(NMOSD)(Akaishi et al.,2020a).

关键词： AQP4 relapse

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Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson J.Michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA department of pediatrics University of CincinnatiCincinnatiOHUSA department of neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

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Imaging mass spectrometry: a molecular microscope for studying the role of lipids in Parkinson's disease

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Neural Regeneration Research 2024年第6期19卷 1179-1180页

作者： Vinata Vedam-Mai Jacob M.Samuel Boone M.Prentice department of neurology University of Florida department of Chemistry University of Florida

Parkinson’s disease–A lipidopathy? The histopathological hallmark of Parkinson’s disease(PD) and dementia with Lewy bodies are inclusions enriched in α-synuclein(α-syn), known as Lewy bodies, which are not only composed of proteins, but also a core of lipid species. PD has been thus far principally thought of as a “proteinopathy” caused by the misfolding of α-syn. However,

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Anti-aquaporin-4 antibody(AQP4-IgG)and anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)in the cerebrospinal fluid

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Neural Regeneration Research 2024年第5期19卷 949-950页

作者： Tetsuya Akaishi Tatsuro Misu department of neurology Tohoku UniversitySendaiJapan

In the last decade,a new neurological disease concept known as anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)-associated disease(MOGAD)has emerged and is currently one of the most focused research areas in the field of neuroimmunology.MOG is a membrane protein mainly expressed on the surface of oligodendrocytes(Zhou et al.,2006).The exact pathogenic role of MOG-IgG in patients with MOGAD remains unclear;however,MOG-IgG has been suggested to cause tissue alterations and damage MOG-expressing cells(Zhou et al.,2006).The pathogenicity of MOG-IgG is further supported by the observation that only a few patients with acquired central nervous system(CNS)demyelinating syndromes exhibit both anti-aquaporin-4 antibody(AQP4-IgG)and MOG-IgG simultaneously,particularly with clear positivity levels of these antibodies as indicated by a cell-based assay result with a titer≥1:100(Sechi et al.,2021;Banwell et al.,2023).

关键词： AQP4 myelin

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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang neurology Beijing Tiantan HospitalBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina department of Medicine and neurology The University of MelbourneMelbourneVictoriaAustralia neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA department of neurology and Comprehensive Stroke Center Massachusetts General HospitalBostonMassachusettsUSA department of neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within 4.5hours.Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond 4.5hours.Methods and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical trial.Patients who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volume6s at 24 hours and NIHSS score change from baseline at 7days.Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.Discussion TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5hours.Trial registration number NCT05141305.

关键词： Therapy random Rational

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Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease

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Neural Regeneration Research 2024年第6期19卷 1197-1198页

作者： Davide Cossu Nobutaka Hatiori department of neurology Juntendo University department of Biomedical Sciences Sassari University

Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolsk...

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Mortality from cerebrovascular diseases in China:Exploration of recent and future trends

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Chinese Medical Journal 2024年第5期137卷 588-595页

作者： Bin Lv Ge Song Feng Jing Mingyu Li Hua Zhou Wanjun Li Jiacai Lin Shengyuan Yu Jun Wang Xiangyu Cao Chenglin Tian department of neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China department of neurology the 305 Hospital of Chinese PLABeijing 100017China department of Internal Medicine Gucheng County Hospital of Traditional Chinese MedicineHengshuiHebei 253800China department of neurology Tangshan Hospital of Traditional Chinese MedicineTangshanHebei 063000China department of neurology Hainan Hospital of Chinese PLA General HospitalSanyaHainan 572013China

Background:Cerebrovascular disease(CVD)ranks among the foremost factors responsible for mortality on a global scale.The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods:We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points(CDC-DSP)system.The mortality of CVD in 2020 was described by age,sex,residence,and region.The temporal trend from 2013 to 2019 was evaluated using joinpoint regression,and estimated rates of decline were extrapolated until 2030 using time series models.Results:In 2019,the age-standardized mortality in China(ASMRC)per 100,000 individuals was 113.2.The ASMRC for males(137.7/10^(5))and rural areas(123.0/10^(5))were both higher when stratified by gender and urban/rural residence.The central region had the highest mortality(126.5/10^(5)),the western region had a slightly lower mortality(123.5/10^(5)),and the eastern region had the lowest mortality(97.3/10^(5)).The age-specific mortality showed an accelerated upward trend from aged 55-59 years,with maximum mortality observed in individuals over 85 years of age.The age-standardized mortality of CVD decreased by 2.43%(95%confidence interval,1.02-3.81%)annually from 2013 to 2019.Notably,the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years.In 2020,both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019.The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030.Conclusion:The heightened focus on the burden of CVD among males,rural areas,the central and western of China,and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities,consequently presenting novel challenges to strategies for disease prevention and control.

关键词： Cerebrovascular diseases Mortality Epidemiology Global Burden of Disease China COVID-19 pandemic

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Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice

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Neural Regeneration Research 2024年第4期19卷 863-871页

作者： Chenlu Zhu Xiao Ren Chen Liu Yawei Liu Yonggang Wang department of neurology Lanzhou University Second Hospital department of neurology The First Affiliated Hospital of Nanchang University department of neurology Xiaogan City Central Hospital Health Service department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China Headache Center Department of NeurologyBeijing Tiantan HospitalCapital Medical University

Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

关键词： Adora2a Alzheimer’s disease astrocyte cAMP signaling pathway dentate gyrus dystrophic neurites microglia neurogenesis plaque Rbm8a

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Use of MLC901 in cerebral venous sinus thrombosis:Three case reports

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World Journal of Clinical Cases 2024年第2期12卷 346-353页

作者： Anita Ante Arsovska Narayanaswamy Venketasubramanian department of Urgent neurology University Clinic of NeurologyUniversity Ss.Cyril and Methodius-Faculty of MedicineSkopje 1000North Macedonia department of neurology Raffles HospitalSingapore 188770Singapore

BACKGROUND Cerebral venous sinus thrombosis(CVT)is rare cause of cerebrovascular disease.The incidence is 0.5%of all stroke.The majority of affected patients are young adults(mean age:35-40 years)with mild to moderate disabilities.Poor outcome with severe disability is seen in 13%of cases.Early diagnosis and treatment are important for good outcomes and preventing complications.Treatment options are limited and mostly based on consensus.NeuroAiD II™(MLC901;Moleac Pte,Ltd,Singapore)has a potential beneficial role in post-stroke recovery,by aiding the natural brain recovery process.CASE SUMMARY MLC901 consists of nine natural herbal ingredients.Studies have shown its safety profile and aid in post stroke recovery.The aim of this case series was to demonstrate the potential role of MLC901 in stroke recovery of patients with cerebral venous sinus thrombosis(CVST)who received MLC901 in addition to standard of care.The prescribed dose of MLC901 is 400 mg/cap two capsules,three times a day.Data from these patients were prospectively collected at baseline and at monthly visits,for a duration of 3 mo.Outcome measures included adherence to therapy,side effects,National Institutes of Health Stroke Scale,Glasgow Coma Scale,modified Rankin Scale,and the Short Orientation-Memory-Concentration Test.MLC901 was well tolerated and no side effects were reported.All patients were stable with improved condition.CONCLUSION This case series highlights the potential therapeutic effects of MLC901 on CVST and provides support for further studies.

关键词： MLC901 Cerebral venous sinus thrombosis Anticoagulation therapy Safety Case report

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