Heavy Ethanol Consumption Aggravates the Ischemic Cerebral Injury by Inhibiting ALDH2. Issue 8 (December 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: 2015-12
• 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

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.