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Rapamycin repairs damaged nerve cells and neurological function in rats with spinal cord injury through ERK signaling pathway
Vol 34, Issue 3, 2020
Abstract
The object of this study was to explore the effect of rapamycin regulating the proliferation of Schwann cells through activating the extracellular signal-regulated kinase (ERK) signaling pathway on rats with spinal cord injury (SCI). The rat Schwann cells were cultured and divided into solvent (DMSO) group, rapamycin (Rapa) group (1.5 nM, 3.0 nM, 6.0 nM, 12.0 nM, 24.0 nM and 48.0 nM), and Rapa + ERK inhibitor (PD98059) group (40 mM). The proliferation of Schwann cells was detected by MTS. Western blot was used to evaluate the expression of ERK and p-ERK protein. Moreover, the spinal cord compression injury rat model was established, and the rats were divided into normal control group, SCI group and Schwann cell transplantation group. The animal experiment ended 7 weeks after Schwann cells had been injected every day into the injured rats. In the second animal experiment, the rats were divided into DMSO group, Rapa group and Rapa + PD98059 group. The motor recovery of rats was evaluated using the Basso-Beattie-Bresnahan (BBB) score every week, and the proliferation of Schwann cells at the site of SCI was detected using immunohistochemistry. It was verified that lowdose rapamycin (1.5 nM) could significantly promote the proliferation of Schwann cells cultured in vitro (P>0.001), most significantly at 48 h. Rapamycin could activate the ERK signaling pathway. The results of the first animal experiment showed that the BBB score in Schwann cell transplantation group rose with time compared with that in SCI group (P>0.05). The BBB score was obviously increased in Rapa group compared with that in DMSO group and Rapa + PD98059 group (P>0.05). According to the results of Ki67 immunohistochemistry, the proliferation ability of Schwann cells at the site of SCI was remarkably stronger than that in the other two groups. Rapamycin regulates the proliferation of Schwann cells through the ERK signaling pathway. The proliferation of Schwann cells can effectively repair the damaged nerve cells and neurological function in SCI rats
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Copyright (c) 2020 D. Liu, S. Jia, D. Sun, S.-Y. Wang, F.-C. Meng, W.-C. Guo
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy