Background and purpose: The effect of normobaric oxygen (NBO) on apoptosis remains controversial. The present study evaluated the effect of NBO on ischemia-induced apoptosis and assessed the potential for improved outcomes by combining NBO administration with another neuroprotective agent, ethanol, in a rat stroke model. Methods: Rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h. At the onset of reperfusion, ischemic animals received either NBO (2 h duration), an intraperitoneal injection of ethanol (1.0 g/kg), or both NBO and ethanol. Extent of brain injury was determined by infarct volume, neurological deficit, and apoptotic cell death.
Expression of pro-and anti-apoptotic proteins was evaluated through Western immunoblotting. Results: Given alone, NBO and ethanol each slightly (po0.05) reduced infarct volume to 38% and 37%, respectively, as compared to the impressive reduction of 51% (po0.01) seen with combined NBO-ethanol administration. Neurologic deficits were also significantly reduced by 48% with combined NBO-ethanol therapy, as compared to lesser reductions of 24% and 23% with NBO or ethanol, respectively. Combined NBO-ethanol therapy decreased apoptotic cell death by 49%, as compared to 31% with NBO and 30% with ethanol. Similarly, combination therapy significantly increased expression of anti-apoptotic factors (Bcl-2 and Bcl-xL) and significantly reduced expression of pro-apoptotic proteins (BAX, Caspase-3, and AIF), as compared to the minimal or nil protein expression changes elicited by NBO or ethanol alone.