title: Dose-related influence of chronic alcohol consumption on cerebral ischemia/reperfusion injury.
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 8 weeks and subjected to a 2-hour middle cerebral artery occlusion (MCAO). We evaluated the brain injury at 24 hours 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/24 h 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/24 h 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.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhao
authors.forename: William G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: Denise M
authors.initials: DM
authors.lastname: Arrick
authors.forename: Wanfen
authors.initials: W
authors.lastname: Xiong
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D000431:Ethanol