康复学报 (Oct 2015)
Electroacupuncture at Quchi and Zusanli Enhances the Proliferation of Cortex and SVZ-derived Neural Stem Cell in Cerebral Ischemia-Reperfusion Injured Rats Via Activation of Notch1 Signaling Pathway
Abstract
Objective:To explore the effects and possible mechanisms of electroacupuncture (EA) at the Quchi (LI11) and Zusanli (ST36) acupints on the proliferation of endogenous neural stem cells in ischemic surrounding cortex and subventricular zone (SVZ) in ischemia-reperfusion injury rats, and then provide experimental basis for clinical application.Methods:Cerebral ischemia and reperfusion injury model was established by modified Zea Longa suture embolism. EA at Quchi and Zusanli of the affected limb for three days and seven days, the neurological deficit, infarct volume as well as the overall behavior of the animals were evaluated. The distribution of Nestin, Vimentin positive cells and co-labeled with Brdu were observed by immunohistochemistry and immuno-fluorescence. The expressions of proteins associated with Notch1 signaling pathway were detected by Western Blotting.Results:①The neurological deficit scores and infarct volume were reduced after EA at the Quchi and Zusanli acupints in ischemia-reperfusion injury rats (P<0.05). ②Catwalk gait analysis showed that at the 3rd and 7th day after acupuncture therapy, the average speed increased and the duration decreased when the rats went through Catwalk channel (P<0.05). ③The numbers of Ki-67, Nestin and Vimentin positive cells in ischemic surrounding cortex and ischemic SVZ region were increased after ischemia-reperfusion injury at 8th day in comparation with 4th day in the model group rats (P<0.05 or P<0.01). The findings of EA treatment for three days and seven days showed that EA could enhance proliferation of neural stem cells (P<0.05). ④The expression of JAG1, NICD, Hes1, Hes5 in ischemic surrounding cortex and ischemic SVZ area were further increased after EA treatment for seven days in comparation with those in the model group (P<0.05 or P<0.01); and in the EA+GSI group, the expression of NICD, Hes1, Hes5 proteins were significantly decreased (P<0.05), but the expression of JAG1 had no significant difference (P>0.05). ⑤In the EA+GSI group, the number of Nestin positive cells and Brdu co-localized with Nestin in ischemic SVZ region were increased (P<0.01 or P<0.05).Conclusions:EA at the Quchi and Zusanli acupints can reduce the infarct volume, improve the overall animal behavior and exert a neuroprotective effect in cerebral ischemia-reperfusion injured rats. The possible mechanism may be activation of the Notch1 signaling pathway resulted in the release of NICD which regulate the expression of Hes1 and Hes5, and thus promote the proliferation of ischemic surrounding cortex area and SVZ-derived neural stem cells.
