Myelin-associated Inhibitory Substrate Components: Role in CNS Regeneration

Abstract

Neurite growth ceases at the end of the developmental period and, in the CNS of higher vertebrates, cannot be reinitiated upon lesion. A persistent intrinsic growth capacity of CNS neurons is present, however, as shown by the local plastic changes of the morphology of dendrites and axonal arborizations in many parts of the nervous system (Purves et al., 1987). Regrowth and long-distance elongation of lesioned, adult CNS neurites can be observed into peripheral nerve pieces implanted into brain, retina, or spinal cord (David and Aguayo, 1981; Benfey et al., 1985; Vidal-Sanz et al., 1987). If peripheral nerves were used as bridges between different regions of the spinal cord, however, the regenerating neurites stopped growing at the site of reentry into the CNS tissue (David and Aguayo, 1981). The long favored hypothesis of insufficient trophic factor supply by the CNS tissue as the reason for this lacking elongation of lesioned CNS tracts (Ramon y Cajal, 1928) has become questionable with the finding that neurons cultured under optimal trophic factor conditions still did not produce processes into optic nerve expiants (Schwab and Thoenen, 1985). In the very same cultures, sciatic nerve expiants were invaded by large numbers of sensory, sympathetic, or retinal axons. The hypothesis of a non-permissive or inhibitory substrate effect exerted by CNS tissue (Schwab and Thoenen, 1985) was supported by experiments with frozen sections as a culture substrate for neurons. Again, drastic differences in neuron adhesion and neurite growth were observed between peripheral nerve and CNS tissues (Carbonetto et al., 1987; Savio and Schwab, 1989). Within the CNS, white matter was much worse as a substrate than gray matter (Savio and Schwab, 1989). Two mechanisms could account for these results: Continued presence in peripheral nerves and absence in the CNS, in particular white matter, of favorable substrate components, or, alternatively, the presence of specific non-permissive or inhibitory substrates in the differentiated CNS tissue.