Role of Wnt/β-catenin in the tolerance to focal cerebral ischemia induced by electroacupuncture pretreatment.

Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/β-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/β-catenin in EA pretreatment-induced neuroprotection. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. Neuronal survival, cell apoptosis, and the Garcia neurological deficit scores were evaluated 24 h after reperfusion. Moreover, learning and memory deficits were assessed 24 h after reperfusion using the Morris water maze test. Finally, the expression of β-catenin and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were investigated in the presence and absence of the Wnt/β-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of β-catenin in the hippocampus 24 h after reperfusion. Moreover, EA pretreatment improved the neurological outcomes, decreased neuronal loss, inhibited apoptosis, and reversed learning and memory deficits following reperfusion. These beneficial effects of EA were attenuated by Dkk-1, which effectively reversed the expression of β-catenin. Furthermore, the administration of a Wnt/β-catenin agonist upregulated the expression of β-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/β-catenin plays a role in the protective effects of EA pretreatment against cerebral ischemia, thus providing evidence of a novel mechanism underlying EA-pretreatment-induced rapid tolerance to focal cerebral ischemia.