Neuroregeneration in the central nervous system

Abstract

Axons in the central nervous system (CNS) in adult mammals do not generally regenerate after damage. It is hypothesized that the lack of axonal regeneration is because of both extrinsic and intrinsic factors. The extrinsic factors would include the insufficient supply of trophic factor and/or neurite growth permissive molecules and the presence of inhibitory molecules in the axons. The intrinsic factor could be the decrease in the axonal growth potential in adult mammals. We have used a series of approaches to alter the extrinsic environment and to enhance the growth potentials of adult axons in the optic nerve and spinal cord. The external environment of the CNS axons could be enhanced by providing an environment suitable for axon regeneration, e.g., through the provision of a conduit using peripheral nerve graft for the damaged axons or Schwann cells or olfactory-ensheathing cell transplantation. We could also neutralize the inhibitory molecules using IN-1 or Nogo receptor blocker or to block inhibitory signaling pathways via Rho pathway inhibitor. The prevention of scar tissue formation by Chondroitinase ABC could also promote axon regeneration in CNS. The intrinsic factors could be modified to enhance regeneration by supplementing appropriate neurotrophic factors, e.g., ciliary neurotrophic factors (CNTF), or by elevating intrinsic regrowth capability, e.g., via the use of cAMP. Our studies suggest that a combined experimental approach is critical in optimizing the regeneration ability of CNS axons in adult mammals.