Neuroprotective effect of WIN 55,212-2 preconditioning against focal cerebral ischemia through activation of extracellular signal-regulated kinases in rats

胡博¹ 王强¹ 陈烨¹ 杜鹃¹ 朱萧玲¹ 吕岩¹ 熊利泽¹ 陈绍洋¹
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University

AIM: It is well documented that cannabinoid receptor agonist WIN 55,212-2 had protective effect against cerebral ischemic injury. Our previous study indicated that WIN 55,212-2 preconditioning induced ischemic tolerance to focal cerebral ischemia in a dose-dependent manner. The present study investigated the time-effect relationship of the WIN 55,212-2 preconditioning and explored the role of phosphorylated extracellular signal-regulated kinase 1/2. METHODS: Rats were pretreated with 1 mg/kg WIN 55,212-2 once a day for 1, 3 and 5 days. Twenty-four hours after the end of pretreatment, focal cerebral ischemia was induced by the middle cerebral artery occlusion. Brain ischemic injury was evaluated by neurological function scores and infarction volumes. The effect of U0126, a potent and specific inhibitor of mitogen-activated protein kinase kinase, on WIN 55,212-2 preconditioning was also studied. Moreover, the expression of phosphorylated extracellular signalregulated kinase 1/2 in the penumbra of ischemic side at 4 h after reperfusion was investigated by immunohistochemistry and Western blotting. RESULTS: The results showed that WIN 55,212-2 preconditioning can protect the rat brain against transient focal cerebral ischemia injury, and the protective effect was enhanced with increased number of preconditioning time, and was partially reversed by U0126. We further found that WIN 55,212-2 preconditioning up-regulated the levels of phosphorylated extracellular signal-regulated kinase 1/2. CONCLUSION: These findings suggest that the neuroprotective effect of WIN 55,212-2 preconditioning against focal cerebral ischemia is through the activation of extracellular signal-regulated kinases in rats.