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脊髓损伤后体外冲击波诱导内源性神经干细胞。

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

机构信息

Department of Orthopedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Spine (Phila Pa 1976). 2018 Feb 15;43(4):E200-E207. doi: 10.1097/BRS.0000000000002302.

Abstract

STUDY DESIGN

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).

SUMMARY OF BACKGROUND DATA

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Collectively, these findings indicate that ESWs on the chronic phase of SCI induce activation of endogenous NSCs and consequent functional improvement.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

动物实验研究

设计目的

本研究旨在探讨体外冲击波(ESW)对脊髓损伤(SCI)后内源性神经干细胞(NSC)增殖的影响。

背景资料概要

外源性干细胞移植治疗 SCI 仍存在许多需要解决的局限性,如理想的细胞来源、移植时机以及移植细胞的命运等。此外,由于 SCI 慢性期的特殊病理状况,其疗效也是另一个问题。

方法

采用 24 只 Sprague-Dawley 大鼠建立挫伤性 SCI 模型,于损伤后 4 周对大鼠进行 ESW 治疗。在 ESW 治疗后 6 周,观察内源性 NSCs(DCX、Sox-2)的增殖和分化以及轴突发芽(GAP-43、MAP-2)。还通过共表达神经元/神经胶质细胞标志物(GFAP、NeuN 和 CC-1)来研究激活的神经干细胞的分化。采用免疫荧光染色和 Western blot 进行定量分析,并与对照组进行比较。临床评估采用 BBB 运动评分量表进行。

结果

实验组内源性神经干细胞的增殖更为明显,这些激活的细胞主要位于中央管的室管膜层和损伤后的后角。在有限数量的细胞中也观察到向神经元和神经胶质细胞的分化。就轴突再生而言,实验组中 GAP-43 和 MAP-2 的表达也明显高于对照组。在 ESW 治疗后 6 周的临床观察期间,通过试验观察到后肢功能得到改善,且无临床恶化。

结论

总之,这些发现表明 ESW 对 SCI 的慢性期诱导内源性 NSCs 的激活,并导致功能改善。

证据水平

无。

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