Retardation of rat sciatic nerve regeneration after local application of minute doses of vincristine.

The effect of vincristine on regeneration of rat sural and tibial nerves following a crush lesion of the sciatic nerve was studied in the pinch test. Vincristine locally applied through an osmotic minipump at the site of the lesion dose-dependently retarded regeneration of the tibial and sural nerve at a threshold dose of 5 ng/day, whereas regeneration was blocked at a dose of 200 ng/day. Regeneration of the sural nerve was more sensitive to the retarding effects of vincristine than was regeneration of the tibial nerve. Systemic weekly administration (i.p.) of 1 mg/kg of vincristine for 7 weeks had approximately the same effect as local application of 10-20 ng/day for 1 week. The differences in sensitivity between sural and tibial nerves and the large discrepancy between local and systemic administration are discussed. On the basis of the potent effects of vincristine used at low concentrations, the absence of overt effects of local vincristine on animal behavior and the short time course in which the local vincristine effects are observed, it is concluded that this paradigm is an extremely suitable model for studying vincristine-induced defects of nervous system function. This model may be used for evaluating the neuroprotective effects of neurotrophic agents against vincristine-induced neuropathies.