| First Author | Li D | Year | 2011 |
| Journal | Exp Neurol | Volume | 230 |
| Issue | 2 | Pages | 302-10 |
| PubMed ID | 21619879 | Mgi Jnum | J:172731 |
| Mgi Id | MGI:5008677 | Doi | 10.1016/j.expneurol.2011.05.009 |
| Citation | Li D, et al. (2011) Adaptation to moderate hypoxia protects cortical neurons against ischemia-reperfusion injury and excitotoxicity independently of HIF-1alpha. Exp Neurol 230(2):302-10 |
| abstractText | Continuous exposure of cultured cortical neurons to moderate hypoxia (1% O(2)) elevates cellular accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha stabilization, also protected neurons against simulated ischemia-reperfusion injury. Nevertheless, genetic deletion of HIF-1alpha 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-1alpha-independent mechanisms, produces strong protective effects against excitotoxic and ischemia-reperfusion related injury. |
