This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Fiori, M. G. Articles by Nunzi, M. G. Search for Related Content PubMed PubMed Citation Articles by Fiori, M. G. Articles by Nunzi, M. G. Social Bookmarking                         What's this?

Peripheral Neuropathy Induced by Intravenous Administration of Vincristine Sulfate in the Rabbit.

An Ultrastructural Study

Postgraduate Program in Nerve Regeneration, Department of Orthopedics, University of Brescia School of Medicine, Brescia, Italy

Antonella Schiavinato

FIDIA Research Laboratories, Abano Terme (PD), Italy

Elisabetta Lini

FIDIA Research Laboratories, Abano Terme (PD), Italy

Maria Grazia Nunzi

Laboratory of Neuromorphology, Biobehavioral Sciences Graduate Degree Program, The University of Connecticut, Box U-154, Storrs, CT 06268, USA

The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic agent vincristine sulfate (VCR) has hampered the correlation between experimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR total dosage similar to that used in humans, a peripheral polyneuropathy characterized by electrophysiological changes that overlap those observed in the clinical setting. The present study was aimed at investigating the ultrastructural features of 3 different nerves (sural, peroneal, and medial gastrocnemius) in rabbits treated with 3 VCR doses that fall within the range (0.2-0.3 mg/kg iv) known to be efficacious chemotherapeutically 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 successful attempts of regeneration and remyelination. Fibers undergoing Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a consequence of ingrowing Schwann cell processes from the adaxonal surface. These ingrowths tended to isolate axoplasmic areas, retaining a fairly normal structure from other areas already crowded with altered organelles and cytoskeletal elements. In any event, neurofibrillary accumulations were rarely seen. These patterns are discussed with reference to those reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripheral neuropathy.

Key Words: Neurotoxicology • Schwann cells • adaxonal ingrowths • axonal degeneration • secondary demyelination • axonal transport • sensory fibers

Toxicologic Pathology, Vol. 23, No. 3, 248-255 (1995)
DOI: 10.1177/019262339502300302


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?