APM OpenIR
Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke
Chen, An-Qi1; Fang, Zhi1; Chen, Xiao-Lu1; Yang, Shuai1; Zhou, Yi-Fan1; Mao, Ling1; Xia, Yuan-Peng1; Jin, Hui-Juan1; Li, Ya-Nan1; You, Ming-Feng1; Wang, Xu-Xia2; Lei, Hao2; He, Quan-Wei1; Hu, Bo1
2019-06-20
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume10Pages:18
AbstractEndothelium (EC) is a key component of bloodbrain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)inhibitor, necrostatin1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microgliainduced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-alpha (TNF-alpha) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFa (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug for stroke therapy.
Funding OrganizationNational Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University
DOI10.1038/s41419-019-1716-9
WOS KeywordCEREBRAL-ARTERY OCCLUSION ; TUMOR-NECROSIS-FACTOR ; PROGRAMMED NECROSIS ; CELL NECROPTOSIS ; PERMEABILITY ; DEATH ; INFLAMMATION ; ACTIVATION ; RATS ; HEMORRHAGE
Language英语
Funding ProjectNational Key Research & Development Program of China[2018YFC1312200] ; National Natural Science Foundation of China[81571119] ; National Natural Science Foundation of China[81400969] ; National Natural Science Foundation of China[81400970] ; National Natural Science Foundation of China[81771249] ; National Natural Science Foundation of China[81671147] ; National Natural Science Foundation of China[81601027] ; National Key Research and Development Program of China[2016YFC1300600] ; National Research Foundation for the Doctoral Program of Higher Education of China[20120142110068] ; New Century Excellent Talents in University[NCET-10-0406]
Funding OrganizationNational Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University ; National Key Research & Development Program of China ; National Key Research & Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; National Research Foundation for the Doctoral Program of Higher Education of China ; New Century Excellent Talents in University ; New Century Excellent Talents in University
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000472435000001
PublisherNATURE PUBLISHING GROUP
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/14485
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorHe, Quan-Wei; Hu, Bo
Affiliation1.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurol, Wuhan, Hubei, Peoples R China
2.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Chen, An-Qi,Fang, Zhi,Chen, Xiao-Lu,et al. Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke[J]. CELL DEATH & DISEASE,2019,10:18.
APA Chen, An-Qi.,Fang, Zhi.,Chen, Xiao-Lu.,Yang, Shuai.,Zhou, Yi-Fan.,...&Hu, Bo.(2019).Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.CELL DEATH & DISEASE,10,18.
MLA Chen, An-Qi,et al."Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke".CELL DEATH & DISEASE 10(2019):18.
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