Induction of Endogenous Neural Stem Cells By Extracorporeal Shock Waves After Spinal Cord Injury.

Abstract

Animal experimental study OBJECTIVES.: The purpose of this study is to investigate the effects of extracorporeal shock waves (ESWs) on endogenous neural stem cells (NSCs) proliferation after spinal cord injury (SCI). Exogenous stem cell transplantation for SCI still has many limitations to be addressed such as ideal cell sources, timing of transplantation, and fate of the transplanted cells. Moreover, the efficacy is another issue owing to a peculiar pathologic condition in the chronic phase of SCI. Contusive SCI was made using 24 Sprague-Dawley rats, and ESWs were applied at post-injury 4 weeks in rats. Proliferation and differentiation of endogenous NSCs (DCX, Sox-2) and axonal sprouting (GAP-43 and MAP-2) were observed at 6 weeks after application of ESWs. Differentiation of the activated neural stem cells was also investigated by coexpression of neuronal/glial cell markers (GFAP, Neu N, and CC-1). Immunofluorescence staining and western blotting were performed for quantitative analysis, and these results were compared with those in the control group. For clinical assessment, the BBB locomotor rating scale was performed. More proliferation of endogenous neural stem cells was noted in the experimental groups, and these activated cells were mainly founded in the ependymal layer of the central canal and the injured posterior horn. Differentiation into neuronal and glial cells was also noted in a limited number of cells. With respect to axonal regeneration, GAP-43 and MAP-2 expressions in the experimental groups were also significantly higher than those in the control group. During 6 weeks' clinical observation following ESWs application, functional improvement of the hindlimb was observed without clinical deterioration by trials. Collectively, these findings indicate that ESWs on the chronic phase of SCI induce activation of endogenous NSCs and consequent functional improvement. N/A.