Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York, USA.
J Neurochem. 2011 Oct;119(1):176-88. doi: 10.1111/j.1471-4159.2011.07370.x. Epub 2011 Aug 16.
The formation of the glial scar following a spinal cord injury presents a significant barrier to the regenerative process. It is primarily composed of chondroitin sulfate proteoglycans (CSPGs) that can inhibit axonal sprouting and regeneration. Although the inhibitory effects on neurons are well documented, little is known about their effects on oligodendrocyte progenitor cells (OPCs). In this study, we examined the effects of CSPGs on OPC process outgrowth and differentiation in vitro. The results show that specific CSPGs, in particularly those highly up-regulated following spinal cord injury, inhibit OPC process outgrowth and differentiation, and that treatment with chondroitinase ABC can completely reverse this inhibition. Additionally, treatment with the Rho kinase inhibitor Y-27632 also reverses the observed inhibition, implicating the activation of Rho kinase in the CSPG inhibition of OPC growth. Taken together, these findings demonstrate that the CSPGs found within the glial scar are not only inhibitory to neurons, but also to OPCs. Moreover, this study shows that chondroitinase ABC treatment, having shown promise in promoting axonal regeneration, may also enhance remyelination.
脊髓损伤后胶质瘢痕的形成对再生过程构成了重大障碍。它主要由软骨素硫酸盐蛋白聚糖（CSPGs）组成，可抑制轴突发芽和再生。尽管其对神经元的抑制作用已有充分的记录，但对其对少突胶质前体细胞（OPCs）的影响知之甚少。在这项研究中，我们研究了 CSPGs 对体外 OPC 突起生长和分化的影响。结果表明，特定的 CSPGs，特别是在脊髓损伤后高度上调的 CSPGs，抑制 OPC 突起生长和分化，而软骨素酶 ABC 的治疗可以完全逆转这种抑制。此外，用 Rho 激酶抑制剂 Y-27632 处理也可以逆转观察到的抑制作用，表明 Rho 激酶的激活参与了 CSPG 对 OPC 生长的抑制作用。综上所述，这些发现表明胶质瘢痕内的 CSPGs 不仅对神经元有抑制作用，对 OPCs 也有抑制作用。此外，本研究表明，软骨素酶 ABC 治疗在促进轴突再生方面显示出前景，也可能增强髓鞘再生。
