Changsuo Liu1, John Weaver, Ke Jian Liu. 1. Brain Imaging Center, Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA.
Abstract
BACKGROUND AND PURPOSE: Normobaric hyperoxia (NBO) has been shown to exert neuroprotective effects against cerebral ischemia and to restore penumbral oxygenation. Inspired by recent reports on postconditioning with intermittent occlusions of cerebral artery, we tested the hypothesis that intermittent NBO (iNBO) may cause oscillation of cerebral oxygenation and thereby elicit repetitive interruptions to reperfusion, leading to attenuated ischemia/reperfusion damage after transient focal cerebral ischemia in rats. METHODS: Rats were subjected to 90 minutes of middle cerebral artery occlusion. During ischemia, animals received air, iNBO (4 cycles of 3 minutes of NBO and 2 minutes of air), continuous NBO (cNBO; 75 minutes), short NBO (18 minutes), or a combination of iNBO and cNBO. Infarct volume and neurological score were evaluated at 24 and 72 hours after ischemia. Production of superoxide was assessed by the hydroethidine method, and the expression of Akt and phosphorylated Akt was examined by Western blot. RESULTS: iNBO and cNBO had similar effects in reducing infarct volume and neurological deficit at 24 hours after ischemia, whereas at 72 hours the neuroprotection exerted by iNBO was greater than cNBO. Combining iNBO and cNBO produced no greater protection, and short NBO failed to provide neuroprotection. Both iNBO and cNBO attenuated superoxide production. Importantly, prolonged activation of Akt was observed in the iNBO group, and neuroprotection by iNBO was partly eliminated by inhibition of Akt activation. CONCLUSIONS: iNBO may represent a novel form of postconditioning, and this neuroprotection is likely mediated by attenuating superoxide generation and activation of the Akt pathway.
BACKGROUND AND PURPOSE: Normobaric hyperoxia (NBO) has been shown to exert neuroprotective effects against cerebral ischemia and to restore penumbral oxygenation. Inspired by recent reports on postconditioning with intermittent occlusions of cerebral artery, we tested the hypothesis that intermittent NBO (iNBO) may cause oscillation of cerebral oxygenation and thereby elicit repetitive interruptions to reperfusion, leading to attenuated ischemia/reperfusion damage after transient focal cerebral ischemia in rats. METHODS:Rats were subjected to 90 minutes of middle cerebral artery occlusion. During ischemia, animals received air, iNBO (4 cycles of 3 minutes of NBO and 2 minutes of air), continuous NBO (cNBO; 75 minutes), short NBO (18 minutes), or a combination of iNBO and cNBO. Infarct volume and neurological score were evaluated at 24 and 72 hours after ischemia. Production of superoxide was assessed by the hydroethidine method, and the expression of Akt and phosphorylated Akt was examined by Western blot. RESULTS: iNBO and cNBO had similar effects in reducing infarct volume and neurological deficit at 24 hours after ischemia, whereas at 72 hours the neuroprotection exerted by iNBO was greater than cNBO. Combining iNBO and cNBO produced no greater protection, and short NBO failed to provide neuroprotection. Both iNBO and cNBO attenuated superoxide production. Importantly, prolonged activation of Akt was observed in the iNBO group, and neuroprotection by iNBO was partly eliminated by inhibition of Akt activation. CONCLUSIONS: iNBO may represent a novel form of postconditioning, and this neuroprotection is likely mediated by attenuating superoxide generation and activation of the Akt pathway.
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