CARBON-DISULFIDE NEUROTOXICITY IN RATS - V - MORPHOLOGY OF AXONAL SWELLING IN THE MUSCULAR BRANCH OF THE POSTERIOR TIBIAL NERVE AND SPINAL-CORD

The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS2) distal axonopathy in the musc ular branch of the posterior tibial nerve (MBPTN) and spinal cord. Mal e and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS2 by in halation, 6 hours/day, 5 days per week, for 2, 4, 8 or 13 weeks. At 8 weeks, in the MBPTN, single fascicles contained individual swollen axo ns. By 13 weeks, multiple fascicles had giant swollen axons with thin myelin sheaths and occasional degenerated and regenerated axons. At 8 weeks, in the spinal cord, white matter changes in cervical segments 1 and 2 consisted of prominent multifocal axonal swelling in the fascic ulus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axo nal swelling was first present at 8 weeks in the lateral and ventro-me dial funiculus. By 13 weeks, axonal swelling was diffuse in the fascic ulus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compare d to the spinal cord, where axonal swelling was present in rats expose d to 800 and 500 ppm, in the muscular branch of the posterior tibial n erve, axonal swelling was only present at 800 ppm at both 8 and 13 wee ks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axon al swelling was not present in the spinal cord at 50 ppm, or in the MB PT at 50 and 500 ppm. Axonal swelling was not present at earlier time points of 2 and 4 weeks in either the spinal cord or MBPTN. (C) 1998 I ntox Press, Inc.