Repair involves all three surfaces of the glial cell

Abstract

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.