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Adaptation to moderate hypoxia protects cortical neurons against ischemia-reperfusion injury and excitotoxicity independently of HIF-1α.
- Source :
-
Experimental neurology [Exp Neurol] 2011 Aug; Vol. 230 (2), pp. 302-10. Date of Electronic Publication: 2011 May 18. - Publication Year :
- 2011
-
Abstract
- Continuous exposure of cultured cortical neurons to moderate hypoxia (1% O(2)) elevates cellular accumulation of hypoxia-inducible factor-1α (HIF-1α) and improves basal survival of cultured cortical neurons. We examined the effects of adaptation to moderate hypoxia on the vulnerability of cultured neurons to the acute injury of simulated ischemia-reperfusion. Cortical neurons cultured continuously in 1% O(2) were markedly protected against simulated ischemia-reperfusion, with protection persisting through 72h after ischemia. Neurons from 1% O(2) conditions were also highly resistant to glutamate-induced NMDA receptor-dependent excitotoxic injury, despite expression of NMDA receptors at levels not significantly changed from controls. Inhibition of prolyl hydroxylase, mimicking cellular signaling effects of hypoxia including HIF-1α stabilization, also protected neurons against simulated ischemia-reperfusion injury. Nevertheless, genetic deletion of HIF-1α expression did not diminish the protection of neurons adapted to 1% O(2) from excitotoxicity or ischemia-reperfusion injury, nor did it prevent the protective effect of prolyl hydroxylase inhibition. We conclude that chronic exposure to moderate hypoxia, through HIF-1α-independent mechanisms, produces strong protective effects against excitotoxic and ischemia-reperfusion related injury.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Analysis of Variance
Animals
Blotting, Western
Cell Survival
Cells, Cultured
Cerebral Cortex physiopathology
Mice
Patch-Clamp Techniques
Reperfusion Injury physiopathology
Cerebral Cortex metabolism
Hypoxia metabolism
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Neurons metabolism
Reperfusion Injury metabolism
Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 230
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 21619879
- Full Text :
- https://doi.org/10.1016/j.expneurol.2011.05.009