CONTACT INHIBITION IN THE FAILURE OF MAMMALIAN CNS AXONAL REGENERATION

Anamniote animals, such as fish and amphibians, are able to regenerate damaged CNS nerves following injury, but regeneration in the mammalia n CNS tracts, such as the optic nerve, does not occur. However, severe d adult mammalian retinal axons can regenerate into peripheral nerve s egments grafted into the brain and this finding has emphasized the imp ortance of the environment in explaining regenerative failure in the a dult mammalian CNS. Following lesions, regenerating axons encounter th e glial cells, oligodendrocytes and astrocytes, and their derivatives, respectively myelin and the astrocytic scar. Experiments to investiga te the influence of these components on axon growth in culture have re vealed cell-surface and extracellular matrix molecules that inhibit ax on extension and growth cone motility. Structural and functional chara cterization of these ligands and their receptors is underway, and may solve the interesting neurobiological conundrum posed by the failure o f mammalian CNS regeneration. Simultaneously, this might allow new pos sibilities for treatment of the severe clinical disabilities resulting from injury to the brain and spinal cord.