Acute administration of ethanol reduces apoptosis following ischemic stroke in rats.

In recent studies, acute ethanol administration appears to play a neuroprotective role during ischemic stroke. We sought to confirm these findings by identifying if ethanol-derived neuroprotection is associated with a reduction in apoptosis. Ethanol at 0.5 and 1.5 g/kg doses was given by intraperitoneal injections to Sprague-Dawley rats after 2h of middle cerebral artery (MCA) occlusion, followed by reperfusion. We quantified apoptotic cell death in each of the treatment groups with ELISA, and measured pro- and anti-apoptotic protein expression with Western blot analysis. Cell death was significantly increased in rats after ischemia and was subsequently significantly reduced by the administration of 1.5 g/kg of ethanol. We found that the 1.5 g/kg dose promoted the expression of pro-survival factors and decreased the expression of apoptotic proteins at 3h after reperfusion. This effect was maintained at 24h for Caspase-3 and apoptosis-inducing factor (AIF), although not for Bcl-2, Bcl-xL, and Bcl-2-associated X (Bax). Administration of 0.5 g/kg of ethanol was not as effective in regulating protein expression as the 1.5 g/kg dose. Our study suggests that administration of ethanol at a dose of 1.5 g/kg after stroke - which provides rat blood alcohol levels equivalent to the legal driving limit - produces a differential protein profile, with increased expression of anti-apoptotic proteins and decrease in pro-apoptotic factors. This results in a significant reduction of neuronal apoptosis and is neuroprotective in ischemia-reperfusion injury.