Neuro-regeneration: plasticity for repair and adaptation.

Abstract

Specificity of connectivity is essential to nervous system function. It is determined by intrinsic programmes of gene expression that define neuronal phenotypes, and by activity-dependent mechanisms. Neuro-regeneration in the adult may involve re-activation of growth programmes within the constraints of neuron-type specific phenotypes. Lesion-induced re-induction of an axonal growth mode in adult neurons correlates with a vigorous cell body reaction that can also lead to apoptotic cell death. Directing the cell body reaction towards regeneration is a major goal towards improving regeneration. Extrinsic factors that prevent axonal regeneration in the adult CNS of higher vertebrates include inhibitory components on the surface of oligodendrocytes and CNS myelin, and proteoglycans associated with scar material; grafts of certain glial cells can promote regeneration. Local nerve sprouting and synaptic plasticity can produce dramatic functional adaptation to lesions in the adult and greatly enhance the impact of the partial regeneration of lesioned axons; nerve sprouting is promoted by diffusible and contact-mediated extrinsic mechanisms, and by intrinsic neuronal components. As a result of recent discoveries, significant progress in promoting axonal regeneration and recovery of function in the adult can be anticipated.