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Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance

文献类型：期刊论文

作者Chen, Min2; Lu, Ting-Jia2; Chen, Xiao-Jing2; Zhou, Yang2; Chen, Qian2; Feng, Xiao-Yan2; Xu, Li2; Duan, Wen-Hu1; Xiong, Zhi-Qi2
刊名STROKE
出版日期2008-11
卷号39期号:11页码:3042-3048
关键词CREB ifenprodil ischemic tolerance NMDA receptor NVP-AAM077 transient global ischemia
ISSN号0039-2499
DOI10.1161/STROKEAHA.108.521898
文献子类Article
英文摘要Background and Purpose-Activation of NMDA subtypes of glutamate receptors is implicated in cell damage induced by ischemia as well as for the establishment of ischemic tolerance after ischemic preconditioning in animal models. We investigated the contributions of NR2A- and NR2B-containing NMDA receptors to ischemic cell death and ischemic tolerance in a rat model of transient global ischemia. Methods-Transient global ischemia was produced in rats by 4-vessel occlusion. Neuronal injury was analyzed by Fluoro-Jade B and Nissl staining. Phosphorylation of CREB was detected by Western blotting and immunohistochemistry. In situ hybridization and reverse transcriptase-polymerase chain reaction were used to evaluate the mRNA level of cpg15 and bdnf. Results-NR2A subtype-specific antagonist NVP-AAM077 enhanced neuronal death after transient global ischemia and abolished the induction of ischemic tolerance. In contrast, NR2B subtype-specific antagonist ifenprodil attenuated ischemic cell death and enhanced preconditioning-induced neuroprotection. Furthermore, selectively blocking NR2A-, but not NR2B-, containing NMDA receptors inhibited ischemia-induced phosphorylation of CREB and the subsequent upregulation of CREB target genes such as cpg15 and bdnf. Conclusions-We found that NR2A- and NR2B- containing NMDA receptor subtypes play differential roles in ischemic neuronal death and ischemic tolerance, suggesting attractive new strategies for the development of drugs for patients with stroke. (Stroke. 2008; 39: 3042-3048.)
WOS关键词TRANSIENT FOREBRAIN ISCHEMIA ; HIPPOCAMPAL CA1 REGION ; SYNAPTIC PLASTICITY ; BRAIN-INJURY ; IN-VITRO ; GERBIL HIPPOCAMPUS ; GENE-EXPRESSION ; RAT-BRAIN ; PATHWAYS ; ACTIVATION
资助项目National Basic Research Program of China[2006CB806600] ; Key State Research Program of China[2006CB943900] ; "863" High-tech Research and Development Program[2006AA02Z166] ; The National Natural Science Foundation of China[30721004] ; Chinese Academy of Sciences[KSCX2-YW-R-099]
WOS研究方向Neurosciences & Neurology ; Cardiovascular System & Cardiology
语种英语
WOS记录号WOS:000260427100022
出版者LIPPINCOTT WILLIAMS & WILKINS
源URL[http://119.78.100.183/handle/2S10ELR8/272774]  
专题药物化学研究室
通讯作者Xiong, Zhi-Qi
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
2.Inst Neurosci, State Key Lab Neurosci, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Chen, Min,Lu, Ting-Jia,Chen, Xiao-Jing,et al. Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance[J]. STROKE,2008,39(11):3042-3048.
APA Chen, Min.,Lu, Ting-Jia.,Chen, Xiao-Jing.,Zhou, Yang.,Chen, Qian.,...&Xiong, Zhi-Qi.(2008).Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance.STROKE,39(11),3042-3048.
MLA Chen, Min,et al."Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance".STROKE 39.11(2008):3042-3048.

入库方式： OAI收割

来源：上海药物研究所

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