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The new era of cardiovascular research:revolutionizing cardiovascular research with 3D models in a dish

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Medical Review 2024年第1期4卷 68-85页

作者： Yuan Yang Hao Yang Fedir N.Kiskin Joe Z.Zhang institute of neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhenGuangdong ProvinceChina institute of neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhen 518132Guangdong ProvinceChina

Cardiovascular research has heavily relied on studies using patient samples and animal ***,patient studies often miss the data from the crucial early stage of cardiovascular diseases,as obtaining primary tissues at this stage is *** animal models can offer some insights into disease mechanisms,although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their *** recent years,a promising breakthrough has emerged in the form of in vitro three-dimensional(3D)cardiovascular models utilizing human pluripotent stem *** innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled *** advancement is pivotal as it addresses the existing gaps in cardiovascular research,allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin *** this review,we first outline various approaches employed to generate these *** then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular condi***,we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and *** their immense potential,challenges persist,particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real ***,overcoming these challenges could revolutionize cardiovascular *** has the potential to offer comprehensive mechanistic insights into human-specific disease processes,ultimately expediting the development of personalized therapies.

关键词： pluripotent stem cells three-dimensional(3D)models cardiac microtissues cardiac organoids vessel organoids organ-on-a-chip

Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical Research Center of neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric DiseasesSoochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology and Clinical Research Center of neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural *** brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and *** the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular *** crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier *** this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain *** review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina Tianjin Geriatrics institute Tianjin Medical University General HospitalTianjinChina Tianjin neurological institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain ***,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains *** this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of *** found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum ***,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured ***,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly *** findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum ***,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan Xia Meng Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese institute for Brain Research BeijingChina National Center for neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry *** estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were *** analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were *** Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were *** adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild *** with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild *** analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year *** BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 ***,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

Development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

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Neuroscience Bulletin 2024年第5期40卷 594-608页

作者： Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao Center for neurological and Psychiatric Research and Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Zhongshan institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan528400China

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug ***,there is an urgent need to develop alternative ***(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug *** it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains *** so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical *** review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.

关键词： Levetiracetam Epilepsy Antiseizure medications Synaptic vesicle protein 2A Brivaracetam Padsevonil

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

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Neural Regeneration Research 2024年第7期19卷 1423-1424页

作者： Jessica Moretti Jennifer Rodger Experimental and Regenerative Neurosciences School of Biological SciencesUniversity of Western AustraliaCrawleyWAAustralia Brain Plasticity Lab Perron Institute for Neurological and Translational ScienceNedlandsWAAustralia

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying *** rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

关键词： stimulation transcranial treatment

Transcranial direct current stimulation efficacy in trigeminal neuralgia

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World Journal of Clinical Cases 2024年第5期12卷 1036-1038页

作者： Theodoros Fasilis Stylianos Gatzonis Panayiotis Patrikelis Stefanos Korfias Athanasia Alexoudi 1^(st) Department of Neurosurgery National and Kapodistrian University of AthensAthens 10676Greece Department of Neurology Neurological Institute of AthensAthens 10676Greece

Trigeminal neuralgia is a severe,disabling pain and its deafferentation remains a challenge for health *** direct current stimulation is a non-invasive stimulation technique which finds new utility in managing ***-fore,the introduction of alternative,non-invasive,safe,and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

关键词： Trigeminal neuralgia Patient-controlled intravenous analgesia Neuromodulation Transcranial direct current stimulation

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

Pseudoaneurysm formation following transarterial embolization of traumatic carotid-cavernous fistula with detachable balloon:An institutional cohort long-term study

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World Journal of Radiology 2024年第4期16卷 94-108页

作者： Prasert Iampreechakul Korrapakc Wangtanaphat Songpol Chuntaroj Yodkhwan Wattanasen Sunisa Hangsapruek Punjama Lertbutsayanukul Pimchanok Puthkhao Somkiet Siriwimonmas Department of Neurosurgery Neurological Institute of ThailandBangkok 10400Thailand Department of Neuroradiology Neurological Institute of ThailandBangkok 10400Thailand Department of Medical Services Neurological Institute of ThailandBangkok 10400Thailand Department of Radiology Bumrungrad International HospitalBangkok 10110Thailand

BACKGROUND The goal of therapy for traumatic carotid-cavernous fistula(TCCF)is the elimination of fistula while maintaining patency of the parent *** treatment for TCCF has evolved from surgery to endovascular management using detachable balloons,coils,liquid embolic agents,covered stents,or flow-diverter stent through arterial or venous *** the withdrawal of detachable balloons from the market in the United States since 2004,transarterial embolization with detachable balloons has currently remained the best initial treatment for TCCF in several ***,the pseudoaneurysm formation following transarterial detachable balloon embolization has rarely been observed in long-term *** To determine the occurrence and long-term follow-up of pseudoaneurysm after transarterial detachable balloon for *** Between January 2009 and December 2019,79 patients diagnosed with TCCF were treated using detachable latex balloons(GOLDBAL)of four *** sizes were stratified into five grades for *** and follow-up assessments involved computed tomography angiography at 1 month,6 month,1 year,and longer intervals for significant *** follow-ups occurred semi-annually for 2 years,then *** analyzed included sex,age,fistula size and location,and balloon *** In our cohort of 79 patients treated for TCCF,pseudoaneurysms formed in 67.1%,with classifications ranging from grade 0 to grade 3;no grade 4 or giant pseudoaneurysms were *** majority of pseudoaneurysms did not progress in size,and some regressed *** developed in most large pseudoaneurysms over 5-10 *** artery occlusion occurred in 7.6%and recurrent fistulas in 16.5%.The primary risk factors for pseudoaneurysm formation were identified as the use of specific balloon sizes,with balloon SP and No.6 significantly associated with its occurrence(P=0.005 and P=0.002,respectively),whereas sex,age,f

关键词： Pseudoaneurysm formation Traumatic carotid-cavernous fistula Direct carotid-cavernous fistula Transarterial embolization Detachable balloon Endovascular treatment Computed tomography angiography Long-term follow-up