Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (19): 3009-3015.doi: 10.3969/j.issn.2095-4344.3538

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Radial extracorporeal shock wave therapy regulates the proliferation and differentiation of neural stem cells in the hippocampus via Notch1/Hes1 pathway after cerebral ischemia

Su Mingzhu1, Ma Yuewen1, 2   

  1. 1The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China; 2Department of Rehabilitation Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
  • Received:2020-05-07 Revised:2020-05-13 Accepted:2020-07-17 Online:2021-07-09 Published:2021-01-13
  • Contact: Ma Yuewen, MD, Professor, Chief physician, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China; Department of Rehabilitation Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
  • About author:Su Mingzhu, Master, Physician, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
  • Supported by:
    the Liaoning Provincial Key Research & Development Guidance Program, No. 2017225013 (to MYW)

Abstract: BACKGROUND: Our previous research found that radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in vitro, and the specific mechanism is related to the upregulation of Notch1 signaling pathway. However, there is no relevant research report on whether the proliferation and differentiation of neural stem cells can also be promoted through this pathway in vivo.
OBJECTIVE: To explore whether radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in hippocampus after cerebral ischemia through Notch1/Hes1 signaling pathway in vivo. 
METHODS:  Rat models of right cerebral ischemia were established by middle cerebral artery occlusion. After successful modeling, the rats were randomly divided into two groups: the radial extracorporeal shock wave therapy group (treatment group) and the control group. In the treatment group, 72 hours after middle cerebral artery occlusion, radial extracorporeal shock wave therapy was directly applied to the right side of the rats’ head at a dose of 0.1 MPa, 200 impulses, and 10 Hz, every three days. In the control group, 72 hours after middle cerebral artery occlusion, the same dose of radial extracorporeal shock wave therapy was given, but the transmitter probe did not touch the head of the rats, only the sound stimulation. Both groups were observed at 12, 21 and 30 days after middle cerebral artery occlusion. Expression levels of nestin, NSE, Notch1 and Hes1 in the ischemic hippocampus of rats were detected by immunohistochemistry, western blot assay, and RT-PCR.
RESULTS AND CONCLUSION: (1) The mNss score of the treatment group was significantly lower than the control group at 12, 21, and 30 days, which indicated that radial extracorporeal shock wave therapy could significantly improve neurological function in rats with cerebral ischemia. (2) Compared with the control group, the expression of Nestin and NSE in ischemic hippocampus of rats increased significantly in the treatment group, which indicated that radial extracorporeal shock wave therapy could promote the proliferation and differentiation of neural stem cells in hippocampus after cerebral ischemia. (3) Compared with the control group, the expression of Notch1 and Hes1 in the ischemic hippocampus of rats in the treatment group was higher than that in the control group, which suggested that radial extracorporeal shock wave therapy could upregulate the expression of Notch1/Hes1 signaling pathway in the hippocampus. (4) The results confirm that radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in the hippocampus after cerebral ischemia, and improve neurological function. The precise mechanism is related to the upregulation of Notch1/Hes1 signaling pathway. 


Key words: stem cells, neural stem cells, radial extracorporeal shock wave therapy, Notch1, signaling pathway, hippocampus, rat

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