The effect of NGF depletion on the neurotropic influence exerted by the distal stump following nerve transection.

Following nerve section, regenerating axons from the proximal stump grow preferentially towards the distal stump. It has been postulated that this may result from the release of a neurotropic factor. To investigate whether the protein nerve growth factor (NGF) plays such a role, we immunised adult rats against NGF and examined the effect on regeneration of sectioned nerves through Y-shaped silastic tubes towards either the distal stump or an empty arm. Regeneration through the tubes was assessed electrophysiologically and the number of myelinated and nonmyelinated fibres at different sites was quantified using electron microscopy. There was electrophysiological evidence of regeneration towards the distal nerve stump in all the animals and there was no significant difference between the immunised and control animals in the size of compound action potential (CAP) ratios. Histologically, the majority of axons were found to have regenerated towards the distal nerve stump in 9/10 of the control animals and 7/9 of the immunised animals and there was no significant difference between the two groups in the numbers of regenerating myelinated or unmyelinated axons. However, in the immunised animals both myelinated and unmyelinated axons were slightly but significantly smaller and the myelin sheaths were thinner than in the control animals. In 2 immunised animals and none of the controls a small CAP was recorded while stimulating distal to the 'empty arm' and the presence of a small number of myelinated and unmyelinated axons was confirmed histologically. We conclude that as depletion of NGF does not block the preferential growth of regenerating axons towards the distal nerve stump it does not play the major neurotropic role in nerve regeneration. The reduction in size and myelin thickness of the regenerated axons after immunisation confirms the neurotrophic effects of NGF.