Heavy ethanol consumption aggravates the ischemic cerebral injury by inhibiting ALDH2. Issue 8 (14th July 2015)

• Record Type: Journal Article
• Authors: Wang, Wei; Lin, Li‐Li; Guo, Jin‐Min; Cheng, Yan‐Qiong; Qian, Jiao; Mehta, Jawahar L.; Su, Ding‐Feng; Luan, Ping; Liu, Ai‐Jun
• Is Part Of: International journal of stroke. Volume 10:Issue 8(2015:Dec.)
• Page Start: 1261
• Page End: 1269
• Publication Date: 2015-07-14
• Subjects: 4‐HNE -- acetaldehyde -- ALDH2 -- heavy ethanol consumption -- ischemic stroke -- risk factor; 616.8005
• DOI: 10.1111/ijs.12560
• Languages: English
• ISSNs: 1747-4930

Abstract

Abstract : Background: Heavy ethanol consumption is widely accepted as a risk for ischemic stroke. The molecular mechanisms of ethanol‐induced brain injury have not been fully understood. Aim: This study aims to find out the mechanism of the ischemic cerebral injury. Methods: We used Sprague‐Dawley rats with transient middle cerebral artery occlusion for acute experiment and stroke‐prone spontaneously hypertensive rats for long‐term experiment in vivo, and oxygen‐glucose deprivation model in vitro to define a detrimental effect of different doses of ethanol on ischemic stroke injury. We also used mitochondrial aldehyde dehydrogenase 2 knockdown/overexpression or inhibitor/activator to investigate mechanism of the adverse effects of ethanol. Results: High‐dose ethanol (36% of calorie derived from ethanol) significantly increased the infarct size in rats ( P < 0·01) and decreased the survival time of stroke‐prone spontaneously hypertensive rats by about 20%. Six‐week treatment with high‐dose ethanol changed a distribution of isoelectric point of aldehyde dehydrogenase 2 and inhibited aldehyde dehydrogenase 2 activity in brain. High dose of ethanol increased the cerebral acetaldehyde level, and increased 4‐hydroxy‐2‐nonenal and malondialdehyde in serum of rats with middle cerebral artery occlusion. The activator of aldehyde dehydrogenase 2, Alda‐1 abolished neuronal cells death and ischemic injury induced by ethanol and the inhibitor reversed the injurious effects. An overexpression of aldehyde dehydrogenase 2 completely abolished the increased infarct size and neurological deficit score by ethanol. Conversely, knockdown of aldehyde dehydrogenase 2 increased the infarct size and exaggerated the cerebral injury induced by ethanol. Conclusions: High concentrations of ethanol aggravate cerebral injury by inhibiting of aldehyde dehydrogenase 2 and inducing excess accumulation of aldehydes.