Role of Notch signaling pathway in cerebral ischemic tolerance induced by electroacupuncture preconditioning

Objective To investigate the role of Notch signaling pathway in cerebral ischemic tolenmce induced by clectroacupuncture (EA) preconditioning.Methods Fifty-two adult male SD rats weighing 280-320 g were randomly divided into 2 groups(n=each):control group(group C)and electroacupuncture preconditionig group(group EA).Group C received no treatment.Group EA received EA at the Baihui acupoint (GV20) for 30 min a day for 5 days.Twenty-four hours after the last preconditionig,focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 120 min,followed by 72 h of reperfusion.Notch intracellular domain(NICD)expression was determined by Western blot and expression of Notch1,Notch4,Jag1,and Hes1 mRNA by real-time PCR immediately before iachemia and 24 and 72 h of reperfusion.The neurological deficit was scored at 72 h of reperfusion.The infarct volumes were then determined after evaluation of the neurological deficit score .Results There was no significant difference in Hesl mRNA and NICD expression immediately before ischemia between group EA and C(P>O.05).NICD expression was up-regulated at 24 and 72 h of reperfusion in both groups, and Hesl mRNA expression at 72 h of reperfusion in group C and at 24 h of reperfusion in group EA was up-regulated compared with those immediately before ischemia (P < 0.05). Hes1 mRNA and NICD expression was up-regulated in group C, while down-regulated in group EA at 72 h of reperfusion compared with those at 24 h of reperfusion ( P < 0.05 ). Compared with group C, the expression of Notchl,Notch4 and Jag1 mRNA was up-regulated immediately before ischemia, and Hes1 mRNA and NICD expression was up-regulated at 24 h of reperfusion while down-regulated at 72 h of reperfusion in group EA( P < 0.05). EA preconditioning significantly reduced infarct volumes and increased neurological deficit scores at 72 h of reperfusion (P < 0.05 ). Conclusion Notch signaling pathway may participate in cerebral ischemic tolerance induced by EA preconditioning. Key words: Receptors, notch; Electroacupuncture; Ischemic preconditioning; Brain; Reperfusion injury