PERIPHERAL NEUROPATHY INDUCED BY INTRAVENOUS ADMINISTRATION OF VINCRISTINE SULFATE IN THE RABBIT - AN ULTRASTRUCTURAL-STUDY

The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic age nt vincristine sulfate (VCR) has hampered the correlation between expe rimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR tota l dosage similar to that used in humans, a peripheral polyneuropathy c haracterized by electrophysiological changes that overlap those observ ed in the clinical setting. The present study was aimed at investigati ng the ultrastructural features of 3 different nerves (sural, peroneal , and medial gastrocnemius) in rabbits treated with 3 VCR doses that f all within the range (0.2-0.3 mg/kg iv) known to be efficacious chemot herapeutically and active neurotoxicologically. Regardless of the dose and the nerve under examination, histopathologic alterations appeared in the form of an overall loss of myelinated fibers, accompanied by s uccessful attempts of regeneration and remyelination. Fibers undergoin g Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a conseque nce of ingrowing Schwann cell processes from the adaxonal surface. The se ingrowths tended to isolate axoplasmic areas, retaining a fairly no rmal structure from other areas already crowded with altered organelle s and cytoskeletal elements. In any event, neurofibrillary accumulatio ns were rarely seen. These patterns are discussed with reference to th ose reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripher al neuropathy.