Influences of Alcohol Consumption on Transient Focal Cerebral Ischemia

Abstract

Ischemic stroke is a leading cause of mortality and long‐term disability. Alcohol is one of the most abused drugs. We examined the dose‐dependent influences of chronic alcohol consumption on transient focal cerebral ischemia. Sprague‐Dawley rats were fed liquid diets with or without alcohol (1%, 3%, 5%, and 6.4% v/v) for 8 weeks. Transient focal cerebral ischemia was induced by a 2‐hour middle cerebral artery occlusion (MCAO). Ischemic area was determined by contrast‐enhanced perfusion‐weighted imaging at the end of MCAO. Ischemic brain damage was evaluated on days 1, 3, and 14. Gene expression profile in peri‐infarct area was measured at 24 hours of reperfusion by DNA microarray. There was no difference in ischemic area between nonalcohol‐fed and alcohol‐fed rats. However, total infarct volume was reduced by 45% in 1% alcohol‐fed rats and increased by 32% in 6.4% alcohol‐fed rats at 24 hours of reperfusion. The protective effect of 1% alcohol consumption and detrimental effect of 6.4% alcohol consumption on transient focal cerebral ischemia could be seen at later time points. 3% and 5% alcohol did not significantly altered total infarct volume. In addition, ischemia/reperfusion induced an upregulation in inflammatory genes. The magnitude of upregulation in intergrin β2 and MMP‐9 was less in 1% alcohol‐fed rats but greater in 6.4% alcohol‐fed rats compared to nonalcohol‐fed rats. Our findings suggest that disparate effects of low and high dose alcohol consumption on ischemic brain damage may be related to an altered inflammatory response.