Perspectives on axonal regeneration in the mammalian CNS

In the CNS of mammals, axonal regeneration is limited by inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth, as well as some properties of so-called 'reactive astrocytes' which make the environment non-permissive for axonal growth, contribute to the inhibitory nature of the mammalian CNS. Furthermore, mechanisms for effective removal or neutralization of inhibitory components of cell debris are lacking in the mature mammalian CNS. However, in a permissive environment, mammalian CNS axons are able to regrow, to recognize target areas and to re-establish functional synapses with target neurones. Moreover, recent observations suggest that guiding molecules, like those required for axon guidance in the developing CNS, become expressed after lesions. Regenerating CNS axons seem to be able to recognize such guidance cues. Thus, even regenerating CNS axons of mammals might ultimately succeed in re-establishing topographically ordered functional synapses in their target regions.