Abstract T P245: Decreased Metallopeptidase and Aquaporin Expressions by Acute Ethanol Administration: A Potential Treatment for Ischemic Stroke?
Introduction: Cerebral ischemia up-regulation of aquaporin (AQP) and metallopeptidase (MMP) expressions is related to increasing blood-brain barrier (BBB) permeability and brain edema. Ethanol (EtOH) has been shown to provide neuroprotective effects. The precise mechanisms by which these effects occur have yet to be elucidated. In this study, we tested the relationship of the neuroprotective effects of EtOH post-stroke with MMP2, MMP9 and AQP4, AQP9 expressions utilizing both in vitro and in vivo models.
Methods: A total of 72 adult male Sprague-Dawley rats were subjected to 2h right middle cerebral artery (MCAO). Different doses of EtOH (0.5 g/kg and 1.5 g/kg) were administered by intraperitoneal injection 2h after stroke. Brain edema estimates were obtained by measuring brain water content. BBB permeability was measured by Evans blue dye assay. Oxygen-glucose deprivation and re-oxygenation (OGD) experiments were performed on whole brain slice cultures. Western-blots were performed to measure protein levels of AQP4, AQP9, MMP9, MMP2, tight junction protein (ZO-1) and basal lamina.
Results: The EtOH treatment dose dependently reduced infarct volume (MCAo: 53.92%±0.03%; EtOH 0.5 g/kg: 50.04%±0.02%;1.5 g/kg: 28.41%±0.02%) compared to the control group. The 1.5 g/kg EtOH treatment significantly decreased lesion volume, BBB leakage (Stroke: 46.8±4.5 ug/g; 1.5 g/kg: 33.5±3.8 ug/g) and brain edema (Stroke: 83.2%±0.3%; 1.5 g/kg: 80.6%±0.8%) compared to the stroke saline-treated group. The EtOH (1.5 g/kg) treatment also significantly reduced the levels of AQP9, AQP4, MMP2 and MMP9 compared to the stroke control group, while no significant difference was observed between the two ethanol treatment groups. Furthermore, in vitro results show reductions in MMP and AQP expressions, induced by EtOH treatment, are associated with elevated ZO-1 and basal lamina levels.
Conclusion: EtOH is an effective neuroprotective therapy identified by the reduction in infarct volume, edema volume, and BBB leakage after stroke. Decreases in MMP2, MMP9, AQP4, and AQP9 expressions may contribute to EtOH-induced neuroprotection.
Author Disclosures: W.A. Li: None. C. Peng: None. M. Guthikonda: None. Y. Ding: None.
This research has received full or partial funding support from the American Heart Association, Midwest Affiliate – Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota, Wisconsin.
- © 2015 by American Heart Association, Inc.