A Selective Cannabinoid CB2 Receptor Agonist Decreases Infarct Volume In A Mouse Middle Cerebral Artery Occlusion/Reperfusion Model

Abstract

Stroke is a major cause of, morbidity and mortality in the United States. It has been shown that leukocyte activation, including rolling and adhesion along the microvascular endothelium, is an essential step in cerebral ischemia/reperfusion injury. The CB2 receptor is primarily expressed by cells of immune system and its activation may provide a potential therapeutic target in ischemia/reperfusion injury. The purpose of this study was to determine if selective CB2 agonist can interfere with leukocyte activation and attenuate ischemia/reperfusion injury. In a double blind experiment, male C56BL/6 mice received either bolus injection of a CB2 agonist (0–3853) at 1mg/kg i.v. or equal volume of vehicle one hour before ischemia. Transient middle cerebral artery occlusion (MCAO) was performed using an intraluminal filament method for one hour followed by 24 hours reperfusion. Cerebral infarct volume was measured by triphenyltetrazolium chloride staining and neurological score was recorded after 24 hours reperfusion. The results demonstrate that CB2 agonist administration reduced infarct volume by approximately 37% and also significantly improved motor function. This project is funded, in part, under a grant with the Pennsylvania Department of Health and supported in part by DA P30 13429.