@article{ref1,
title="Heavy ethanol consumption aggravates the ischemic cerebral injury by inhibiting ALDH2",
journal="International journal of stroke",
year="2015",
author="Wang, Weixu and Lin, Li-Li and Guo, Jin-Min and Cheng, Yan-Qiong and Qian, Jiao and Mehta, Jawahar L. and Su, Ding-Feng and Luan, Ping and Liu, Ai-Jun",
volume="10",
number="8",
pages="1261-1269",
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. <br><br>AIM: This study aims to find out the mechanism of the ischemic cerebral injury. <br><br>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. <br><br>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. <br><br>CONCLUSIONS: High concentrations of ethanol aggravate cerebral injury by inhibiting of aldehyde dehydrogenase 2 and inducing excess accumulation of aldehydes.<p /> <p>Language: en</p>",
language="en",
issn="1747-4930",
doi="10.1111/ijs.12560",
url="http://dx.doi.org/10.1111/ijs.12560"
}