Neuro-regeneration: plasticity for repair and adaptation

• 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. • Asa result of recent discoveries, significant progress in promoting axonal regeneration and recovery of function in the adult can be anticipated.