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Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats.
Neuroscience Bulletin ( IF 5.6 ) Pub Date : 2019-11-16 , DOI: 10.1007/s12264-019-00442-0
Gang Li 1, 2 , Zhong-Kai Fan 3 , Guang-Fei Gu 1, 2 , Zhi-Qiang Jia 4 , Qiang-Qiang Zhang 3 , Jun-Yu Dai 3 , Shi-Sheng He 1, 2
Affiliation  

Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.

中文翻译:

硬膜外脊髓刺激通过增强少突胶质细胞的存活和分化以及通过保护大鼠脊髓损伤后的髓磷脂来促进运动功能的恢复。

硬膜外脊髓刺激(ESCS)可以显着改善脊髓损伤(SCI)后的运动和感觉功能,但其潜在机制尚不清楚。在这里,我们调查了ESCS是否会影响SCI大鼠的少突胶质细胞分化及其细胞和分子机制。ESCS改善SCI后7天,14天,21天和28天的后肢运动功能。ESCS还可以在28天时显着增加髓鞘区域,并在7天时减少脊髓白质中凋亡细胞的数量。SCI在7天时降低2',3'-环核苷酸3'-磷酸二酯酶(CNPase,少突胶质细胞标记)的表达,而在28天时降低髓鞘碱性蛋白的表达。ESCS在7天时显着上调了这些标志物,并增加了Sox2 / CNPase / DAPI阳性细胞(新分化的少突胶质细胞)的百分比。重组人骨形态发生蛋白4(rhBMP4)在ESCS后显着下调了这些因子。此外,ESCS显着降低SCI后BMP4和p-Smad1 / 5/9的表达,而rhBMP4降低ESCS的这种作用。这些发现表明,ESCS通过抑制SCI后的BMP4-Smad1 / 5/9信号通路,提高了少突胶质细胞的存活和分化,保护了髓鞘并促进了运动功能的恢复。
更新日期:2019-11-16
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