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CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

Neural Regeneration Research 2024年第1期19卷 196-204页

作者： Xiang Chen Yuwan Lin Zhiling Zhang Yuting Tang Panghai Ye Wei Dai Wenlong Zhang Hanqun Liu Guoyou Peng Shuxuan Huang Jiewen Qiu Wenyuan Guo Xiaoqin Zhu Zhuohua Wu Yaoyun Kuang Pingyi Xu Miaomiao Zhou department of neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of neurology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of neurology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's ***-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy ***,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea ***,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of *** found that CHCHD2 protected mitochondria from developing MPP^(+)-induced *** normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase *** addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and *** weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this *** findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

关键词： ATP synthase(F1F0-ATPase) coiled-coil helix coiled-coil helix domain containing 2 dopaminergic neuron mitochondrial dysfunction neurodegeneration oligomycin sensitivity-conferring protein Parkinson's disease T61I mutation tyrosine hydroxylase

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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 *** plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolski et al.,2022).Mo...

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Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder

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Neuroscience Bulletin 2024年第8期40卷 1104-1114页

作者： Man Chen Yun‑Hui Chu Wen‑Xiang Yu Yun‑Fan You Yue Tang Xiao‑Wei Pang Hang Zhang Ke Shang Gang Deng Luo‑Qi Zhou Sheng Yang Wei Wang Jun Xiao Dai‑Shi Tian Chuan Qin department of neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and TechnologyWuhan 430030China department of neurology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China

Neuromyelitis optica spectrum disorder(NMOSD)is an autoimmune inflammatory demyelinating disease of the central nervous system(CNS)accompanied by blood-brain barrier(BBB)*** in microglial lipid metabolism is believed to be closely associated with the neuropathology of ***,there is limited evidence on the functional relevance of circulating lipids in CNS demyelination,cellular metabolism,and microglial ***,we found that serum low-density lipoprotein(LDL)was positively correlated with markers of neurological damage in NMOSD *** addition,we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB,directly activating *** activation leads to excessive phagocytosis of myelin debris,inhibition of lipid metabolism,and increased glycolysis,ultimately exacerbating myelin *** also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in *** findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage,highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

关键词： Neuromyelitis optica spectrum disorder Low-density lipoprotein Microglia

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Postoperative abdominal herpes zoster complicated by intestinal obstruction:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1138-1143页

作者： Zhen-Yu Dong Rui-Xian Shi Xiao-Biao Song Ming-Yue Du Ji-Jun Wang department of general Surgery Baotou Central HospitalBaotou 014040Inner Mongolia Autonomous RegionChina department of general Surgery Baotou Medical CollegeBaotou 014040Inner Mongolia Autonomous RegionChina department of neurology Baotou Central HospitalBaotou 014040Inner Mongolia Autonomous RegionChina department of neurology Inner Mongolia Medical UniversityHohhot 010110Inner Mongolia Autonomous RegionChina

BACKGROUND Intestinal obstruction is a common occurrence in clinical ***,the occurrence of herpes zoster complicated by intestinal obstruction after abdominal surgery is exceedingly *** the diagnostic and treatment process,clinicians consider it crucial to identify the primary causes of its occurrence to ensure effective treatment and avoiding *** SUMMARY Herein,we present the case of a 40-year-old female patient with intestinal obstruction who underwent laparoscopic appendectomy and developed herpes zoster after *** the patient's clinical manifestations and relevant laboratory tests,it was suggested that the varicella zoster virus reactivated during the latent period after abdominal surgery,causing herpes ***,the herpes virus invaded the visceral nerve fibers,causing gastrointestinal dysfunction and loss of intestinal peristalsis,which eventually led to intestinal *** patient was successfully treated through conservative treatment and antiviral therapy and subsequently discharged from the *** Pseudo-intestinal obstruction secondary to herpes zoster infection is difficult to distinguish from mechanical intestinal obstruction owing to various *** cases of inexplicable intestinal obstructions,considering the possibility of a viral infection is essential to minimize misdiagnosis and missed diagnoses。

关键词： Herpes zoster Pseudo-intestinal obstruction Ogilvie syndrome Peripheral motor neuropathy Case report

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Intra-arterial tenecteplase during thrombectomy for acute stroke(BRETIS-TNK II):rationale and design

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Stroke & Vascular neurology 2024年第1期9卷 59-65页

作者： Zi-Ai Zhao Jing Qiu Wei Li Thanh Nguyen Shouchun Wang Huaizhang Shi Ming Wei Feng Wang Di Li Hui-Sheng Chen department of neurology General Hospital of Northern Theater CommandShenyangLiaoning ProvinceChina neurology RadiologyBoston Medical CenterBostonMassachusettsUSA department of neurology First Affiliated Hospital of Jilin UniversityChangchunJilinChina department of Neurosurgery First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina department of Neurosurgery Tianjin Huanhu HospitalTianjinTianjinChina department of Interventional Therapy First Affiliated Hospital of Dalian Medical UniversityDalianChina Neurological Intervention department Dalian Municipal Central HospitalDalianLiaoningChina

Background Our recent pilot study suggests intra-arterial tenecteplase(TNK)during the first pass of endovascular treatment(EVT)seems safe,may increase first-pass reperfusion and good outcome in acute ischaemic stroke(AIS)patients with large-vessel occlusion(LVO).Aims To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom *** size estimates A maximum of 380 patients are required to test the superiority hypothesis with 80%power according to a two-side 0.05 level of significance,stratified by age,gender,baseline systolic blood pressure,prestroke modified Rankin Scale(mRS),baseline National Institute of Health stroke scale,baseline ASPECTS,time from onset to groin puncture,intravenous thrombolysis before EVT,stroke territory and stroke *** Intra-arterial TNK during thrombectomy for acute stroke(BRETIS-TNK II)study is a prospective,randomised,adaptive enrichment,open-label,blinded end point,multicentre *** AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:*** experimental group will be treated with intra-arterial infusion of TNK during *** control group will be treated with standard *** The primary end point is a favourable outcome,defined as an mRS score of 0–2 at 90 *** primary safety end point is symptomatic intracranial haemorrhage within 48 hours,which is defined as an increase in the National Institutes of Health Stroke Scale score of≥4 points as a result of the intracranial *** The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

关键词： rational stratified TNK

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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

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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

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International standard of Traditional Chinese Medicine Techniques: Traditional Chinese Medicine guidelines for acute primary headache(2022)

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Journal of Traditional Chinese Medicine 2024年第4期44卷 839-850页

作者： YAO Yuning CAO Kegang ZHANG Genming LIU Jianping CHEN Wei CAO Junling YANG Wenming YAN Yongmei GENG Chang JU Yi ZHAO Dexi QU Miao LI Xiaoli SUN Li HAN Zhenyun HE Liyun CUI Fangyuan FU Caihong ZHOU Bo LIAO Shuqin department of neurology Dongzhimen Hospital of Beijing University of Chinese MedicineBeijing 100007China Centre for Evidence-Based Chinese Medicine Beijing University of Chinese MedicineBeijing 100029Chin Encephalopathy center First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031China department of neurology Affiliated Hospital of Shaanxi University of Chinese MedicineXi'an 710077China department of neurology Beijing Changping District Hospital of Traditional Chinese MedicineBeijing 102299China neurology center Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China department of neurology Affiliated Hospital of Changchun University of Chinese MedicineChangchun 130021China department of neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin department of neurology Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China department of Geriatrics Jilin Academy of Traditional Chinese MedicineChangchun 130012China department of neurology Shenzhen Hospital of Beijing University of Chinese MedicineShenzhen 518172China Institute of Basic Research in Clinical Medicine China Academy Of Chinese Medical SciencesBeijing 100700Chin department of Rehabilitation Shunyi HospitalBeijing Traditional Chinese Medicine HospitalBeijng 101300China department of neurology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To summarize the evidence from Traditional Chinese Medicine(TCM)practice in the treatment of acute primary headache and provide clinical practice ***:The guidelines were developed in accordance with the World Health Organization guideline development *** the establishment of steering committee,panel and the registration and protocol formulation,the evidence on TCM for acute primary headache from published guidelines,clinical evidence,and expert experience and consensus were *** grading of recommendations assessment,development and evaluation method was used to grade the evidence and make the ***:Based on the available evidence,the guidelines recommended three TCM herbal decoctions,six Chinese patent medicines,and two kinds of external application of Chinese herbal *** recommendations based on the expert experience and consensus were also included in the ***:TCM diagnosis and treatment of decoction,Chinese patent medicine and external application for treating acute primary headache were *** hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.

关键词： medicine,Chinese traditional acute primary headache practice guideline

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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 *** incidence is 0.5%of all *** majority of affected patients are young adults(mean age:35-40 years)with mild to moderate *** outcome with severe disability is seen in 13%of *** diagnosis and treatment are important for good outcomes and preventing *** options are limited and mostly based on *** II™(MLC901;Moleac Pte,Ltd,Singapore)has a potential beneficial role in post-stroke recovery,by aiding the natural brain recovery *** SUMMARY MLC901 consists of nine natural herbal *** have shown its safety profile and aid in post stroke *** 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 *** prescribed dose of MLC901 is 400 mg/cap two capsules,three times a *** from these patients were prospectively collected at baseline and at monthly visits,for a duration of 3 *** 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 ***901 was well tolerated and no side effects were *** patients were stable with improved *** 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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Neuronal trafficking as a key to functional recovery in immune-mediated neuropathies

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Neural Regeneration Research 2024年第11期19卷 2331-2332页

作者： Felix Kohle Michael Schroeter department of neurology University of Cologne and University Hospital CologneCologneGermany

Immune-mediated neuropathies are rare diseases of the peripheral nervous system(PNS),substantially affecting patients’functionality and quality of *** are amenable to immunomodulatory treatments,which in many cases stabilize disease progression,but long-term deficits persist in many *** long-term deficits are particularly observed in monophasic autoimmune neuropathies like Guillain-Barrésyndrome and also in chronic variants,e.g.,chronic inflammatory demyelinating neuropathy(Fadia et al.,2019).

关键词： diseases autoimmune

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