RESUMO
A previous study has demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. In the present study, we investigated whether adenosine receptor 1 (A1 R) is involved in EA pretreatment-induced cognitive impairment after focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min in male Sprague-Dawley rats. The neurobehavioral score, cognitive function [as determined by the Morris water maze (MWM) test], neuronal number, and the Bax/Bcl-2 ratio was evaluated at 24 h after reperfusion in the presence or absence of CCPA (a selective A1 receptor agonist), DPCPX (a selective A1 receptor antagonist) into left lateral ventricle, or A1 short interfering RNA into the hippocampus area. The expression of the A1 receptor in the hippocampus was also investigated. The result showed that EA pretreatment upregulated the neuronal expression of the A1 receptor in the rat hippocampus at 90 min. And EA pretreatment reversed cognitive impairment, improved neurological outcome, and inhibited apoptosis at 24 h after reperfusion. Pretreatment with CCPA could imitate the beneficial effects of EA pretreatment. But the EA pretreatment effects were abolished by DPCPX. Furthermore, A1 receptor protein was reduced by A1 short interfering RNA which attenuated EA pretreatment-induced cognitive impairment.
RESUMO
Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/ß-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/ß-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 ß-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/ß-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of ß-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 ß-catenin. Furthermore, the administration of a Wnt/ß-catenin agonist upregulated the expression of ß-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/ß-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.