Acute administration of ethanol reduces apoptosis following ischemic stroke in rats

• Acute ethanol administration after ischemia creates an anti-apoptotic profile.
• Pro-survival proteins are elevated while apoptotic factors are suppressed.
• Neuroprotection is dose-dependent with 1.5 g/kg ethanol being most effective.
• Ethanol's effect on apoptotic factors is most clearly seen at 3 h after reperfusion.
• Apoptotic cell death is significantly reduced by 1.5 g/kg ethanol at 24 h.

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 2 h 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 3 h after reperfusion. This effect was maintained at 24 h 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.