Department of Cell and Developmental Biology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Exp Neurol. 2011 Sep;231(1):19-29. doi: 10.1016/j.expneurol.2011.05.002. Epub 2011 May 8.
Following spinal cord injury (SCI), the demyelination of spared intact axons near the lesion site likely contributes to the loss of motor function. This demyelination occurs when oligodendrocytes, the myelinating cells of the central nervous system (CNS), are either destroyed during the initial trauma or die as a result of secondary pathology. In an attempt to remyelinate the affected axons, endogenous oligodendrocyte progenitor cells (OPCs) begin to accumulate at the border of demyelination. However, the differentiation of OPCs into fully myelinating cells is limited. While the reasons for this are unknown, it is well known that the injured spinal cord is rich in inhibitory molecules that block repair. One such family of molecules is the chondroitin sulfate proteoglycans (CSPGs), which are known to be highly inhibitory to the process of axonal elongation. Recent in vitro findings have demonstrated that CSPGs are also highly inhibitory to OPCs, affecting both their migration and differentiation. Treatment with the enzyme chondroitinase ABC (cABC), which removes the glycosaminoglycan side chains of CSPGs, reverses the inhibitory effects of CSPGs on these cells. In the present study, we examined the effects of cABC on the migratory behavior of endogenous OPCs in vivo following a moderate spinal contusion injury. The total number of OPCs surrounding the lesion site was significantly increased after cABC treatment as compared to controls. cABC treatment also enhanced axonal sprouting, but OPC migration occurs along a different time course and appears independent of new process outgrowth. These data suggest that CSPGs in the post-injury environment inhibit the migration of OPCs, as well as axonal regeneration. Therefore, cABC treatment may not only enhance regenerative axonal sprouting, but may also enhance remyelination after SCI.
脊髓损伤（SCI）后，病变部位附近未受损的完整轴突脱髓鞘可能导致运动功能丧失。这种脱髓鞘发生在少突胶质细胞（中枢神经系统的髓鞘形成细胞）在最初的创伤中被破坏或因继发性病变而死亡时。为了使受影响的轴突重新髓鞘化，内源性少突胶质前体细胞（OPC）开始在脱髓鞘边界处聚集。然而，OPC 分化为完全髓鞘化细胞的能力有限。虽然原因尚不清楚，但众所周知，受伤的脊髓富含抑制修复的抑制性分子。软骨素硫酸盐蛋白聚糖（CSPGs）就是这样一类分子，它们被认为对轴突伸长过程具有高度抑制作用。最近的体外研究结果表明，CSPGs 对 OPC 也具有高度抑制作用，影响其迁移和分化。用酶软骨素酶 ABC（cABC）处理，该酶可去除 CSPGs 的糖胺聚糖侧链，可逆转 CSPGs 对这些细胞的抑制作用。在本研究中，我们在中度脊髓挫伤损伤后体内研究了 cABC 对内源性 OPC 迁移行为的影响。与对照组相比，cABC 处理后损伤部位周围的 OPC 总数显著增加。cABC 处理还增强了轴突发芽，但 OPC 迁移的时间过程不同，似乎与新突起的生长无关。这些数据表明，损伤后环境中的 CSPGs 抑制了 OPC 的迁移和轴突再生。因此，cABC 治疗不仅可以增强再生轴突发芽，还可以增强 SCI 后的髓鞘形成。
