Acute ethanol treatment reduces blood-brain barrier dysfunction following ischemia/reperfusion injury

Background and purpose: Ethanol has been shown to provide neuroprotective effects, but the precise mechanisms by which these effects occur have yet to be investigated. In this study, we investigate blood brain barrier (BBB) and edema level changes in association with expression of matrix metalloproteinases (MMP-2 and MMP-9) and aquaporins (AQP-4 and AQP-9) in ethanol treated rats following middle cerebral artery (MCA) occlusion. Methods: An ischemic stroke model was generated by occlusion of the right MCA for 2 h in male Sprague Dawley rats (n=72). Edema levels and BBB integrity following the ischemic event were studied by quantification of brain water content and extravasadon of Evans blue following 24 and 48 h of reperfusion, respectively. Expression of the proteins MMP-2 and MMP-9, as well as AQP-4 and AQP-9, were determined by Western blot analysis 3 and 24 h after reperfusion. Results: Treatment with ethanol significantly reduced brain edema (P<0.01) and BBB dysfunction (P<0.05) when compared to the saline-treated control groups. The upregulation of MMP-2 and MMP-9, as well as AQP-4 and AQP-9, following ischemia/reperfusion, was significantly reduced in ethanol-treated groups (P<0.05). Conclusions: Ethanol ameliorates brain edema and BBB disruption after stroke, in association with a reduction in the expression of MMPs and AQPs. These results provide clues to ethanol's neuroprotective properties. (C) 2011 Elsevier B.V. All rights reserved.