title: Carbon disulfide neurotoxicity in rats: V. Morphology of axonal swelling in the muscular branch of the posterior tibial nerve and spinal cord.
abstract: The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS2) distal axonopathy in the muscular branch of the posterior tibial nerve (MBPTN) and spinal cord. Male and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS2 by inhalation, 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 axons. 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 fasciculus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axonal swelling was first present at 8 weeks in the lateral and ventro-medial funiculus. By 13 weeks, axonal swelling was diffuse in the fasciculus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compared to the spinal cord, where axonal swelling was present in rats exposed to 800 and 500 ppm, in the muscular branch of the posterior tibial nerve, axonal swelling was only present at 800 ppm at both 8 and 13 weeks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axonal swelling was not present in the spinal cord at 50 ppm, or in the MBPT 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.
authors.affiliation: Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Sills
authors.forename: G J
authors.initials: GJ
authors.lastname: Harry
authors.forename: D L
authors.initials: DL
authors.lastname: Morgan
authors.forename: W M
authors.initials: WM
authors.lastname: Valentine
authors.forename: D G
authors.initials: DG
authors.lastname: Graham
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D002246:Carbon Disulfide / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008161:Lumbosacral Region / Q000294:innervation; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D009333:Neck / Q000294:innervation; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D013979:Tibial Nerve / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D002246:Carbon Disulfide