Institute of Neurology, University College London, London, UK.
Prog Brain Res. 2012;201:199-218. doi: 10.1016/B978-0-444-59544-7.00010-X.
We propose that severed adult CNS axons are intrinsically capable of regeneration and reestablishing lost functions and that the key to repair lies in reconfiguring the scarring response of the astrocytic network. Astrocytes are multifunctional cells with three distinct surfaces: a glia to glial surface, providing the junctions needed to incorporate the astrocytes into the network; a glia to mesodermal surface, at which astrocytes collaborate with the meningeal fibroblasts to maintain the protective covering of the CNS; and a glia to neuronal surface, which provides the routes along which axons travel. After injury, the astrocytes collaborate with the meningeal fibroblasts to form a scar, which provides the necessary defensive sealing of the opened surface of the CNS, but which also has the detrimental effect of closing off the pathways along which axons could regenerate. Incorporation of glial cells transplanted from the olfactory system into a CNS injury causes a re-arrangement of the scarred astrocyte/fibroblast complex so as to produce the alignment of the glia to neuronal surfaces needed to provide a pathway for the regeneration of severed axons. Olfactory ensheathing cells certainly have a direct stimulatory effect on axons, but without concomitant reorganization of the glial scar, this could not in itself lead to regeneration of severed axons to their targets.
我们提出,已切断的成人中枢神经系统轴突具有内在的再生能力,并能重新建立失去的功能,而修复的关键在于重新配置星形胶质细胞网络的瘢痕反应。星形胶质细胞是具有三种不同表面的多功能细胞:胶质细胞到胶质细胞的表面,提供将星形胶质细胞整合到网络中所需的连接;胶质细胞到中胚层的表面,星形胶质细胞与脑膜成纤维细胞合作,以维持中枢神经系统的保护覆盖物;以及胶质细胞到神经元的表面,它提供了轴突行进的路径。受伤后,星形胶质细胞与脑膜成纤维细胞合作形成瘢痕,为开放的中枢神经系统表面提供必要的防御性密封,但也有不利影响,即关闭了轴突可以再生的路径。将嗅球系统中移植的神经胶质细胞整合到中枢神经系统损伤中,会导致瘢痕星形胶质细胞/成纤维细胞复合物的重新排列,从而产生需要的胶质细胞到神经元表面的排列,为切断的轴突的再生提供途径。嗅鞘细胞肯定对轴突有直接的刺激作用,但如果没有同时对神经胶质瘢痕进行重组,这本身就不能导致切断的轴突再生到其靶标。