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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 *** in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s *** 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 *** 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 ***,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this *** 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 *** sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein *** 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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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 *** mortality patterns of CVDs and temporal trends in China need to be well-illustrated and ***:We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points(CDC-DSP)*** mortality of CVD in 2020 was described by age,sex,residence,and *** temporal trend from 2013 to 2019 was evaluated using joinpoint regression,and estimated rates of decline were extrapolated until 2030 using time series ***:In 2019,the age-standardized mortality in China(ASMRC)per 100,000 individuals was *** ASMRC for males(137.7/10^(5))and rural areas(123.0/10^(5))were both higher when stratified by gender and urban/rural *** 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-standardized mortality of CVD decreased by 2.43%(95%confidence interval,1.02-3.81%)annually from 2013 to ***,the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 *** 2020,both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in *** estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in ***: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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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 *** 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 *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** 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 *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** 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 *** registration number NCT05141305.

关键词： Therapy random Rational

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Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

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Neural Regeneration Research 2024年第11期19卷 2430-2443页

作者： Siji Wang Qianyan He Yang Qu Wenjing Yin Ruoyu Zhao Xuyutian Wang Yi Yang Zhen-Ni Guo Stroke Center Department of Neurologythe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience Research Center Department of Neurologythe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of Breast Surgery General Surgery Centerthe First Hospital of Jilin UniversityChangchunJilin ProvinceChina

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical *** emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron *** neural stem cells are beneficial not only in cell replacement but also through the bystander *** stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/***,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain *** this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem *** hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

关键词： bystander effect cell replacement extracellular vesicles ischemic stroke neural stem cells neural stem cell engineering

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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 *** 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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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang department of neurology The First Affiliated Hospital of Ningbo University department of general Surgery The First Affiliated Hospital of Ningbo University department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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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 *** 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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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 *** is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following *** evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced *** 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 ***,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 *** found that as mice aged,Rac1 expression declined in the *** 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–*** was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by *** 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 ***,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 *** 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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Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 131-136页

作者： Ioannis Giachos Spyridon Doumazos Anastasia Tsiogka Konstantina Manoli George Tagaris Tryfon Rotsos Vassilios Kozobolis Ioannis Iliopoulos Marilita Moschos First department of Ophthalmology National and Kapodistrian University of Athens Medical SchoolAthens 11527Greece department of neurology General Hospital of Athens“Georgios Gennimatas”Athens 11527Greece department of Ophthalmology Faculty of MedicineSchool of Health SciencesUniversity of PatrasPatras 26504Greece neurology department Democritus University of ThraceAlexandroupolis 68100Greece

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology department of the general Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was *** 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the *** foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with *** coherence tomography(OCT)was used to measure macular *** statistical analysis was conducted by using a mixed effect linear regression ***:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)***-VD and fDCP-VD didn’t approach statistical *** FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)*** didn’t approach statistical *** retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with *** findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

关键词： Parkinson’s disease optical coherence tomography angiography retinal vascular density foveal avascular zone

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