Hypoxic preconditioning prevents cortical infarction by transient focal ischemia-reperfusion

Anya M.Y. Lin*, Shiang Wen Dung, Chau Fong Chen, Wen Han Chen, Low Tone Ho

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

One of the proposed pathologic actions underlying brain infarction is excess free radicals resulting from reoxygenation. In this paper we report an investigation of the neuroprotective effect of hypoxic preconditioning on transient focal ischemia-reperfusion injuries in rat brain. Female Wistar rats were subjected to 380 mmHg in an altitude chamber for 15 hours/day. Our ex vivo studies showed that auto-oxidation and iron-induced lipid peroxidation of brain homogenates of the four-week hypoxia-preconditioned rats were significantly lower than those of the normoxic rats. A focal infarction in the cerebral cortex of normoxic rats was consistently observed 24 hours after a 60-minute transient ischemic occlusion of the right middle cerebral artery and bilateral common carotid arteries. Hypoxic preconditioning in fact attenuated cortical infarction in a duration-dependent manner. Induction of the neuroprotection required two weeks of hypoxic preconditioning. Four weeks of hypoxic preconditioning significantly reduced the cortical infarcted area, the elevated lipid peroxidation, and resulted in an acute increase in cytosolic cytochrome c in the infarcted cortex of normoxic rats. The protective effect of four weeks of hypoxic preconditioning lasted seven days under a renormoxic condition. Our data suggest that oxidative stress may result in apoptosis in the transient focal ischemia-reperfusion injuries. Furthermore, hypoxic preconditioning attenuated cortical infarction in the rat brain. Although supplementation of antioxidants may encounter difficulty at the blood-brain barrier, hypoxic preconditioning is very likely to protect CNS targets from oxidative injuries without any barrier.

Original languageEnglish
Pages (from-to)168-178
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume993
DOIs
StatePublished - 2003

Keywords

  • Hypoxic preconditioning
  • Oxidative stress
  • Transient focal ischemia-reperfusion injury

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