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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

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

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

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 *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric *** 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 *** 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 *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** 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 *** children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited *** 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 *** 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

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

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Zoological Research 2024年第4期45卷 857-874页

作者： Na Zhao Xiu Chen Qiu-Gu Chen Xue-Ting Liu Fan Geng Meng-Meng Zhu Fu-Ling Yan Zhi-Jun Zhang Qing-Guo Ren department of neurology School of MedicineSoutheast UniversityNanjingJiangsu 210009China department of neurology Affiliated Zhongda HospitalSoutheast UniversityNanjingJiangsu 210009China

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive ***,the underlying mechanisms remain *** the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic *** findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the *** with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived ***,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic ***,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau ***,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive ***,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

关键词： Chronic sleep deprivation Tau pathology NLRP3 inflammasome Autophagy GSK-3β Microbiota-gut-brain axis

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

Fate of Right Coronary Artery Occlusion after a Surgically Repaired Aorto- Ventricular Tunnel in a Neonate

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Congenital Heart Disease 2024年第3期19卷 267-273页

作者： Sherif Negm Loic Mace Fedoua El Louali Beatrice Desnous Philipe Aldebert Virginie Fouilloux Marien Lenoir department of pediatric Cardiac Surgery Hôpital Timone enfantAssistance Public-Hopitaux MarseilleAix-Marseille UniversitéMarseilleFrance department of Cardiothoracic Surgery Tanta UniversityTantaEgypt department of pediatric Cardiology Hôpital Timone enfantAssistance Public-Hopitaux MarseilleAix-Marseille UniversitéMarseilleFrance department of neurology Hôpital Timone enfantAssistance Public-Hopitaux MarseilleAix-Marseille UniversitéMarseilleFrance

The aorto-ventricular tunnel is a rare congenital cardiac *** present a case of aorto-ventricular tunnel diagnosed via fetal *** surgery was performed on the 2nd day of life to close the tun-nel,located just in front of the right coronary ostium,due to the patient’s unstable health *** post-operative period revealed complete occlusion of the right coronary *** to the patient’s stability,we opted not to reintervene on the right coronary *** patient fully recovered without the need for further coronary *** cases of patients with an aorto-ventricular tunnel(AVT)and associated coronary lesions,it is crucial to exercise caution when intervening in the coronary arteries.

关键词： Aorto-ventricular tunnel aorta right coronary artery

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours(HOPE):protocol for a randomised,controlled,multicentre study

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Stroke & Vascular neurology 2024年第3期9卷 318-323,I0274-I0282页

作者： Zhongyu Luo Ying Zhou Yaode He Shenqiang Yan Zhicai Chen Xuting Zhang Yi Chen Lu-Sha Tong Wansi Zhong Haitao Hu Kemeng Zhang Jiansheng Yang Bruce C V Campbell Min Lou department of neurology Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina department of Medicine and neurology Melbourne Brain Centre at Royal Melbourne HospitalParkvilleVictoriaAustralia

Background While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke(AIS)within 4.5hours of symptom onset,there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic *** To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5–24hours after stroke onset(for stroke with unknown onset time,the midpoint of the time last known to be well and symptom recognition time;for wake-up stroke,the midpoint of the time last known to be well or sleep onset and wake up time)will benefit from intravenous *** HOPE is a prospective,multicentre,randomised,open-label blinded endpoint trial with the stage of phase *** treatment allocation employs 1:1 *** treatment arm under investigation is alteplase with standard therapy,the control arm is standard *** imaging criteria include ischaemic core volume≤70mL,penumbra≥10mL and mismatch≥20%.Study outcomes The primary outcome is non-disabled functional outcome(assessed as modified Rankin Scale score of 0–1 at 90 days).Discussion HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5–24hours,which has the potential to extend time window and expand eligible population for thrombolysis therapy.

关键词： patients intravenous centre

Next-generation regenerative therapy for ischemic stroke using peripheral blood mononuclear cells

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Neural Regeneration Research 2024年第11期19卷 2341-2342页

作者： Masato Kanazawa Itaru Ninomiya Yutaka Otsu Masahiro Hatakeyama department of neurology Brain Research InstituteNiigata UniversityNiigataJapan

Stroke is the second leading cause of death and the third leading cause of disability worldwide after heart *** predict that stroke deaths and permanent disabilities will increase worldwide by the year ***-target therapies may be insufficient,because ischemic cerebral injury involves several ***-mediated therapies are ideal,because they target multiple cell types to enhance protection and recovery.

关键词： ischemic death cerebral