Dose-Related Influence of Chronic Alcohol Consumption on Cerebral Ischemia/Reperfusion Injury

Honggang Zhao, William G. Mayhan, Denise M. Arrick, Wanfen Xiong, Hong Sun

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: We examined the dose-related influence of alcohol consumption on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism that accounts for the disparate effects of high-dose and low-dose alcohol consumption on cerebral I/R injury. Methods: Sprague-Dawley rats were fed a liquid diet with or without 1, 3, 5, or 6.4% (v/v) alcohol for 8weeks and subjected to a 2-hour middle cerebral artery occlusion (MCAO). We evaluated the brain injury at 24hours of reperfusion. In addition, we measured protein expression of NMDA receptor and excitatory amino acid transporters (EAATs) in parietal cortex and the effect of NMDA receptor antagonist, memantine, on 2-hour MCAO/24h reperfusion-induced brain injury. Results: Compared with non-alcohol-fed rats, the total infarct volume was not altered in 3 and 5% alcohol-fed rats but significantly reduced in 1% alcohol-fed rats and exacerbated in 6.4% alcohol-fed rats. Expression of the NMDA receptor subunit, NR1, was upregulated in 6.4% alcohol-fed rats, whereas expression of EAAT2 was downregulated in 6.4% alcohol-fed rats and upregulated in 1% alcohol-fed rats. Memantine reduced 2-hour MCAO/24h reperfusion-induced brain injury in non-alcohol-fed and 6.4% alcohol-fed rats, but not in 1% alcohol-fed rats. The magnitude of reduction in the brain injury was greater in 6.4% alcohol-fed rats compared to non-alcohol-fed rats. Conclusions: Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury, whereas chronic consumption of high-dose alcohol has detrimental effect on cerebral I/R injury. The disparate effects of low-dose and high-dose alcohol consumption on cerebral I/R may be related to an alteration in NMDA excitotoxicity.

Original languageEnglish (US)
Pages (from-to)1265-1269
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number7
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Alcohol
  • Brain
  • Excitatory Amino Acid Transporter
  • Ischemia
  • NMDA Receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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