Acta Anatomica Sinica ›› 2020, Vol. 51 ›› Issue (1): 15-20.doi: 10.16098/j.issn.0529-1356.2020.01.003

• Neurobiology • Previous Articles     Next Articles

Effect of Notch signaling pathway on nerve regeneration after cerebral ischemia in rats with neural stem cells transplantation#br#

LIU Zong-xiu1,2 ZHANG Zi-wei2 CHENG Yuan2 JIN Xiao-fei2 ZHOU Xiao-hong2 GAO Wei-juan2*   

  1. 1. Department of Pathophysiology, Chengde Medical College, Hebei Chengde 067000, China; 2. Hebei Key Laboratory of Chinese Medicine Basic Research on Prevention and Treatment of Cardio-cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050091, China
  • Received:2019-01-09 Revised:2019-02-16 Online:2020-02-06 Published:2020-04-21
  • Contact: GAO Wei-juan E-mail:gwj6088@163.com

Abstract:

Objective To investigate the mechanism of inhibiting the Notch signaling pathway in promoting neural regeneration after neural stem cells (NSCs) transplantation in rats with cerebral ischemia.  Methods The model of focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) method . NSCs were cultured in vitro and transplanted into the striatum ischemic area. In the experiment, 40 SD rats were divided into sham operation group, model group, transplantation group (transplanted neural stem cells), and N-[N-(3,5-difluorohenacetyl)-L-alanyl]-S-phenylglycinet-butyl ester(DAPT)+ transplantation group. The degree of neuronal damage in each group was observed by HE staining. The expressions of Notch1, Hes1 and Hes5 in the brain tissue of each group were detected by immunohistochemistry and Western blotting.  Results Compared with the sham operation group, the neuron injury in the model group was severe, and nuclear pyknosis and nuclear lysis were observed. The Notch1, Hes1 and Hes5 positive cells increased significantly, and the expression of Notch1, Hes1 and Hes5 proteins were significantly up-regulated (P<0.05). Compared with the model group, the neuronal damage in the transplantation group and the DAPT+ transplantation group were all relieved, and the Notch1, Hes1 and Hes5 positive cells were partially expressed, and the expression of each protein decreased (P<0.05). The DAPT+ transplantation group neurons were compared. The damage was obviously restored, and the expression of protein-positive cells and protein further decreased (P<0.05).  Conclusion Inhibition of Notch signaling pathway can promote nerve regeneration after neural stem cell transplantation in rats with cerebral ischemia. The mechanism is mainly related to down-regulation of Notch1, Hes1 and Hes5 expression.

Key words:  Cerebral ischemia, Neural stem cell transplantation, Nerve regeneration, Notch signaling pathway, HE staining, Rat

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