Regeneration-permissive glia after spinal cord injury

摘要 中枢神经系统（CNS）轴突的有限再生是CNS损伤后恢复的主要障碍。 在确定促进轴突生长的神经元内在机制方面取得了重大进展，但 再生轴突仍然需要一个允许生长的环境。尽管星形胶质细胞的疤痕 被认为是轴突再生的主要抑制屏障，越来越多的证据表明，在某些 在某些条件下，反应性星形胶质细胞可能有助于而不是抑制损伤部位轴突的再生。一 一种可能的解释是，星形胶质细胞瘢痕中存在星形胶质细胞， 可以抑制轴突再生的亚群和可以允许轴突再生的其他亚群。一个潜在 这些再生允许星形胶质细胞的来源是少突胶质细胞祖细胞（OPCs），我们和 其他人已经显示在脊髓损伤（SCI）后可以分化成星形胶质细胞。由于这种分化 能力仅限于胶质瘢痕区域中约10-20%的OPCs，我们假设增加OPCs的数量 OPC衍生的星形胶质细胞可以通过增加再生许可的数量来增强轴突再生， 穿过受损的脊髓。

ABSTRACT Limited regeneration of central nervous system (CNS) axons is a major barrier to recovery after CNS injury. Major advances have been made in identifying neuron-intrinsic mechanisms to promote axonal growth, but regenerating axons still require an environment that is growth-permissive. Although the astroglial scar has been considered to be a major inhibitory barrier to axon regeneration, there is mounting evidence that in certain conditions, reactive astrocytes may aid, rather than inhibit, regeneration of axons across the injury site. One possible explanation that might reconcile these conflicting roles of the astroglial scar is that there are astrocyte subpopulations that can inhibit, and other subpopulations that can permit, axon regeneration. One potential source of these regeneration-permissive astrocytes is oligodendrocyte progenitor cells (OPCs), which we and others have shown can differentiate into astrocytes after spinal cord injury (SCI). Since this differentiation capacity is limited to about 10-20% of OPCs in the glial scar region, we hypothesize that enhancing the number of OPC-derived astrocytes can enhance axon regeneration by increasing the amount of regeneration-permissive substrate across the injured spinal cord.