Electroacupuncture pretreatment induces the tolerance against focal cerebral ischemia through activation of Notch pathway
赵昱1 侯丽宏1 马磊1 朱正华1 朱萧玲1 王强1 吕岩1 陈绍洋1
第四军医大学西京医院麻醉科
Background：Electroacupancture(EA) pretreatment can induce the tolerance against focal cerebral ischemia, however, the underlying mechanisms have not been fully investigated. More and more findings suggest that Notch signaling may be involved in the pathological changes that occur in cerebral ischemia. In this study, we tested the hypothesis that the tolerance against focal cerebral ischemia induced by EA pretreatmentis mediated by Notch signaling.
Methods：Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male adult rats that were unpretreated or pretreated with EA. The mRNA levels of Notch1, Notch4, Jag1 and Hes1 in striatum and hippocampus were evaluated by real-time PCR. The level and the histologic localization of Notch1 NICD in striatum were tested by Western blot and double immunofluorescence staining, respectively. Intraventricular injections with the γ-secretase inhibitor were used to suppress the activation of Notch pathway. Neurobehavioral evaluation and infarct assessment were performed.
Results：Before ischemia, EA pretreatment significantly enhanced Notch1、Notch4 and Jag1 gene transcriptions in the striatum. After ischemia and reperfusion, Hes1 mRNA and Notch1 NICD level in ischemic striatum in EA pretreatment group increased and reached the peak at 2h, 24h, respectively, earlier than those in control group. Intraventricular injection with the γ-secretase inhibitor(MW167) attenuated the neuroprotective effect of EA pretreatment.
Conclusions：Electroacupuncture pretreatment induces the tolerance against focal cerebral ischemia through activation of Notch pathway.
