Cannabinoid Receptor Type 2 Activation Yields Delayed Tolerance to Focal Cerebral Ischemia

Lei      Ma; Zhenghua      Zhu; Yu      Zhao; Lihong      Hou; Qiang      Wang; Lize      Xiong; Xiaoling      Zhu; Ji      Jia; Shaoyang      Chen

doi:10.2174/156720211795495394

Abstract

We demonstrated in our previous research that pretreatment with electroacupuncture (EA) induces rapid (2h after EA) and delayed (24h after EA) tolerance to focal cerebral ischemia. We further elucidate the endocannabinoid and cannabinoid receptor type 1(CB1) are involved in the rapid ischemic tolerance induced by EA pretreatment. The present study aimed at investigating the involvement of the cannabinoid receptor type 2 (CB2) in the neuroprotection conferred by EA pretreatment. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min at 2h and 24h following EA pretreatment in male Sprague-Dawley rats, respectively. Cerebral ischemic injury was evaluated by neurobehavioral scores and infarction volume percentages 72h after reperfusion in the presence or absence of AM251, a selective CB1 receptor antagonist, and AM630, a selective CB2 receptor antagonist. The expression of CB1 and CB2 receptor in the striatum of ischemic hemisphere was also evaluated. The rapid and delayed ischemic tolerance induced by EA pretreatment was reversed by AM251 and AM630 respectively. CB2 receptor expression was up-regulated in the striatum of rat brains at 24h after EA stimuli. These results indicate that CB2 receptor contributed to the delayed neuroprotective effect whereas CB1 receptor to the rapid ischemic tolerance induced by EA pretreatment against focal cerebral ischemia in rats.

Keywords: CB2 receptor, cerebral ischemia, electroacupuncture, pretreatment, Cannabinoid, endocannabinoid, reperfusion, EA stimuli, AM251, Sprague-Dawley, striatum, CB1, rats