Hypoxic Preconditioning Protects against Ischemic Brain Injury

被引：115
作者：
Sharp F.R. [1 ,2 ,3 ,4 ]
Ran R. [1 ,2 ,3 ,4 ]
Lu A. [1 ,2 ,3 ,4 ]
Tang Y. [1 ,2 ,3 ,4 ]
Strauss K.I. [3 ]
Glass T. [2 ]
Ardizzone T. [1 ,2 ,3 ,4 ]
Bernaudin M. [5 ]
机构：
[1] Neuroscience Program, University of Cincinnati, Cincinnati
[2] UMR 6551 Centre National de la Recherche Scientifique, Université de Caen, IFR 47, Caen
来源：
NeuroRX | 2004年 / 1卷 / 1期
基金：
美国国家卫生研究院;
关键词：
EPO; erythropoietin; HIF; Hypoxia; hypoxia-inducible factor; ischemia; oxygen; preconditioning; stress proteins; stroke; VEGF;
D O I：
10.1602/neurorx.1.1.26
中图分类号：
学科分类号：
摘要：
Animals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3 hours) are protected against cerebral and cardiac ischemia between 1 and 2 days later. This hypoxia preconditioning requires new RNA and protein synthesis. The mechanism of this hypoxia-induced tolerance correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-1α and constitutive HIF-1β proteins that bind to the hypoxia response elements in a number of HIF target genes. Our recent studies show that HIF-1α correlates with hypoxia induced tolerance in neonatal rat brain. HIF target genes, also induced following hypoxia-induced tolerance, include vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes. Some or all of these genes may contribute to hypoxia-induced protection against ischemia. HIF induction of the glycolytic enzymes accounts in part for the Pasteur effect in brain and other tissues. Hypoxia-induced tolerance is not likely to be equivalent to treatment with a single HIF target gene protein since other transcription factors including Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression. Understanding the mechanisms and genes involved in hypoxic tolerance may provide new therapeutic targets to treat ischemic injury and enhance recovery. © 2004 The American Society for Experimental NeuroTherapeutics, Inc.
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页码：26 / 35
页数：9
相关论文
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