Antecedent Ethanol Attenuates Cerebral Ischemia/Reperfusion‐induced Leukocyte‐Endothelial Adhesive Interactions: Role of Large Conductance, Ca2+‐activated K+ Channels (BKCa)

Abstract

Our recent work indicates that ethanol ingestion (EtOH‐PC) 24 hrs prior to induction of cerebral ischemia/reperfusion (I/R) reduces postischemic neuronal injury. In this study, we investigated whether EtOH‐PC would reduce I/R‐induced leukocyte‐endothelial adhesive interactions in pial postcapillary venules, and if so, whether this protective effect was triggered by BKCa channel activation. To address this aim, C57BL6 mice were administered ethanol by gavage [(body weight (in g) ×0.6) + 0.3] or treated with the BKCa channel opener, NS‐1619 (0.1mg/kg, ip) 24 hrs prior to I/R in the absence or presence of the BKCa channel blocker, paxilline (PX; 2.5 mg/kg body wt, i.p., administered 10 min before ethanol or NS1619 administration). 24 hour later, both common carotid arteries (CCA) were occluded for 20 min followed by 2 and 3 hours of reperfusion, then the numbers of rolling (LR) and adherent (LA) leukocytes were quantified in pial venules using intravital microscopy. I/R induced large increases in LR and LA in pial venules compared with sham. The increased LR and LA were prevented by EtOH‐PC or antecedent NS1619 administration. These protective effects were attenuated by PX treatment coincident with ethanol or NS1619 administration. Our results indicate that EtOH‐PC may activate BKCa to prevent cerebral ischemia/reperfusion‐induced leukocyte‐endothelial adhesive interactions. Supported by R01AA014945 from NIH