title: Acute administration of ethanol reduces apoptosis following ischemic stroke in rats.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Fu
authors.forename: Changya
authors.initials: C
authors.lastname: Peng
authors.forename: Jamie Y
authors.initials: JY
authors.lastname: Ding
authors.forename: Karam
authors.initials: K
authors.lastname: Asmaro
authors.forename: Jonathon M
authors.initials: JM
authors.lastname: Sullivan
authors.forename: Murali
authors.initials: M
authors.lastname: Guthikonda
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D002545:Brain Ischemia / Q000473:pathology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D020521:Stroke / Q000473:pathology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D000431:Ethanol