IDPN IMPAIRS POSTTRAUMATIC REGENERATION OF RAT SCIATIC-NERVE

The role played by cytoskeletal proteins in nerve regeneration was inv estigated in a model in which the axonal transport of neurofilaments ( NF) is almost selectively impaired. The administration of beta, beta'- iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induce s an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spati al segregation of NF from microtubules (MT). We investigated post-axot omy regeneration of rat sciatic nerve following IDPN administration. C hanges induced by IDPN, as examined in the proximal and distal nerve s tump at 15 and 30 days after lesion, consisted of a statistically sign ificant reduction of the mean axonal diameter (P<0.0001) as compared t o control rats. In addition, the number of regenerating myelinated fib res was smaller in dosed rats (P<0.001) 15 days after crush, whereas a t the later stage the number of axons approached that of control anima ls. Electrophysiological investigation revealed a delay in target rein nervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF (P<0.001), while the number of MT was s lightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alt eration of other components of cytoskeletal proteins, impairs the long itudinal and radial growth of regenerating myelinated axons and confir m that the number of NF is the major determinant of the cross-sectiona l area of each segment of the axon.