The CB₁ antagonist, SR141716A, is protective in permanent photothrombotic cerebral ischemia

Modulation of the endocannabinoid system has been shown to have a significant impact on outcomes in animal models of stroke. We have previously reported a protective effect of the CB₁ antagonist, SR141716A, in a transient reperfusion mouse model of cerebral ischemia. This protective effect was in part mediated by activation of the 5HT_1A receptor. Here we have examined its effect in a mouse model of permanent ischemia induced by photoinjury. The CB₁ antagonist was found to be protective in this model. As was the case following transient ischemia reperfusion, SR141716A (5 mg/kg) resulted in smaller infarct fractions and stroke volumes when utilized both as a pretreatment and as a post-treatment. In contrast to the effect in a transient ischemia model, the pretreatment effect did not depend on the 5HT_1A receptor. Neurological function correlated favorably to the reduction in stroke size when SR141716A was given as a pretreatment. With the incidence of stroke predicted to rise in parallel with an ever aging population, understanding mechanisms underlying ischemia and therapeutics remains a paramount goal of research.