, Volume 1, Issue 1, pp 26–35 | Cite as

Hypoxic preconditioning protects against ischemic brain injury

  • Frank R. SharpEmail author
  • Ruiqiong Ran
  • Aigang Lu
  • Yang Tang
  • Kenneth I. Strauss
  • Todd Glass
  • Tim Ardizzone
  • Myriam Bernaudin


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.

Key Words

Hypoxia preconditioning hypoxia-inducible factor HIF VEGF erythropoietin EPO ischemia stroke oxygen stress proteins 


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2004

Authors and Affiliations

  • Frank R. Sharp
    • 1
    • 2
    • 3
    • 4
    • 6
    Email author
  • Ruiqiong Ran
    • 1
    • 2
    • 3
    • 4
  • Aigang Lu
    • 1
    • 2
    • 3
    • 4
  • Yang Tang
    • 1
    • 2
    • 3
    • 4
  • Kenneth I. Strauss
    • 3
  • Todd Glass
    • 2
  • Tim Ardizzone
    • 1
    • 2
    • 3
    • 4
  • Myriam Bernaudin
    • 5
  1. 1.Department of NeurologyUniversity of CincinnatiCincinnati
  2. 2.Department of PediatricsUniversity of CincinnatiCincinnati
  3. 3.Department of NeurosurgeryUniversity of CincinnatiCincinnati
  4. 4.Department of Neuroscience ProgramUniversity of CincinnatiCincinnati
  5. 5.UMR 6551 Centre National de la Recherche ScientifiqueUniversité de CaenCaenFrance
  6. 6.Departments of Neurology and PediatricsUniversity of Cincinnati, Vontz Center for Molecular Studies Room 2327Cincinnati

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