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.
引用
收藏
页码：26 / 35
页数：9
相关论文
共 164 条
  • [51] Bernaudin M., Tang Y., Reilly M., Petit E., Sharp F., Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance, J Biol Chem, 277, pp. 39728-39738, (2002)
  • [52] Heurteaux C., Lauritzen I., Widmann C., Lazdunski M., Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning, Proc Natl Acad Sci USA, 92, pp. 4666-4670, (1995)
  • [53] Lasley R., Anderson G., Mentzer Jr. R., Ischaemic and hypoxic preconditioning enhance postischaemic recovery of function in the rat heart, Cardiovasc Res, 27, pp. 565-570, (1993)
  • [54] Tang Y., Lu A., Aronow B., Sharp F., Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease, Ann Neurol, 50, pp. 699-707, (2001)
  • [55] Tang Y., Lu A., Aronow B., Wagner K., Sharp F., Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia, Eur J Neurosci, 15, pp. 1937-1952, (2002)
  • [56] Tang Y., Nee A., Lu A., Ran R., Sharp F., Blood genomic expression profile for neuronal injury, J Cereb Blood Flow Metab, 23, pp. 310-319, (2003)
  • [57] Massa S., Longo F., Zuo J., Wang S., Chen J., Sharp F., Cloning of rat grp75, an hsp70-family member, and its expression in normal and ischemic brain, J Neurosci Res, 40, pp. 807-819, (1995)
  • [58] Kietzmann T., Krones-Herzig A., Jungermann K., Signaling cross-talk between hypoxia and glucose via hypoxia-inducible factor 1 and glucose response elements, Biochem Pharmacol, 64, pp. 903-911, (2002)
  • [59] Krones A., Jungermann K., Kietzmann T., Cross-talk between the signals hypoxia and glucose at the glucose response element of the L-type pyruvate kinase gene, Endocrinology, 142, pp. 2707-2718, (2001)
  • [60] Massa S., Swanson R., Sharp F., The stress gene response in brain, Cerebrovasc Brain Metab Rev, 8, pp. 95-158, (1996)
12345678910