Article

The possible mechanism of electroacupuncture promoting hippocampal neural stem cells proliferation in rats with focal cerebral ischemia-reperfusion via activation of Notch signaling pathway

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Abstract

Objective: To investigate the effect of electroacupuncture (EA) promoting hippocampal neural stem cells (NSCs) proliferation in rats with focal cerebral ischemia- reperfusion (I/R) via Notch pathway and to clarify the possible mechanism of EA in treatment of cerebral ischemia. Method: Fifty- four male adult SD rats were randomly divided into the sham operation control group (SC group), the ischemia model group (IC group) and the electroacupuncture group (EA group). Middle cerebral artery occlusion (MCAO) was performed to establish the focal cerebral I/R injury model. Proliferation of hippocampal NSCs in cerebral I/R injured rats was determined by nestin immunohistochemical staining. The expressions of Notch1 and intracellular domain of Notch(NICD) were detected by Western blotting and RT- PCR. The serum level of vascular endothelial growth factor (VEGF) was measured using enzyme-linked immunosorbent assay (ELISA). Result: EA at Quchi (LI11) and Zusanli (ST36) acupoints alleviated neurological deficits significantly and promoted the proliferation of hippocampal NSCs (IC vs EA: 173.40±38.76 vs 246.80±47.73, P=0.028) in cerebral I/R injured rats; enhanced the expressions of Notch1 and NICD, crucial signaling molecules in Notch signaling pathway, and increased the secretion of VEGF. Conclusion: The up-regulatory effect of EA on Notch signaling pathway and neurotrophic factor secretion may result in the promotion of NSCs proliferation and consequently provide the therapeutic effect on cerebral ischemia.

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... Acupuncture points Quchi (LI11) and Zusanli (ST36) are most commonly used in the treatment of post-stroke hemiplegia. Our previous studies suggested that acupuncture at these sites promoted proliferation and differentiation of endogenous neural stem cells in rat models of middle cerebral artery ischemia reperfusion (Chen et al., 2014). Additionally, acupuncture at Quchi and Zusanli enhanced expression of brain derived neurotrophic factor (BDNF) and glial cellderived neurotrophic factor (GDNF) (Ye et al., 2014) and inhibited apoptosis (He et al., 2015), thereby promoting the recovery of motor function through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) (He et al., 2015), Tolllike receptor 4/nuclear factor kappa B (TLR4/NF-κB) (He et al., 2016), extracellular regulated protein kinases (ERK) (He et al., 2015), and Notch signaling pathways (Chen et al., 2014). ...
... Our previous studies suggested that acupuncture at these sites promoted proliferation and differentiation of endogenous neural stem cells in rat models of middle cerebral artery ischemia reperfusion (Chen et al., 2014). Additionally, acupuncture at Quchi and Zusanli enhanced expression of brain derived neurotrophic factor (BDNF) and glial cellderived neurotrophic factor (GDNF) (Ye et al., 2014) and inhibited apoptosis (He et al., 2015), thereby promoting the recovery of motor function through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) (He et al., 2015), Tolllike receptor 4/nuclear factor kappa B (TLR4/NF-κB) (He et al., 2016), extracellular regulated protein kinases (ERK) (He et al., 2015), and Notch signaling pathways (Chen et al., 2014). Other studies have reported that acupoint stimulation increases functional recovery in the hemiplegic limb by regulating the excitability of the cerebral cortex (Maioli et al., 2006;Zunhammer et al., 2012). ...
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