Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal degeneration.
J Neuropathol Exp Neurol 1977 Mar/Apr; 36(2):276-299
The effects of n-hexane (110543), methyl-n-butyl-ketone (591786) (MBK), and 2,5-hexanedione (110134) (HD) on the peripheral nervous system (PNS) were examined in Sprague-Dawley-rats. For n-hexane, rats inhaled 400 to 600 parts per million (ppm) for 1 to 23 weeks or received subcutaneous (sc) injection of 650 to 2000 milligrams per kilogram (mg/kg) 5 days per week for up to 35 weeks. For MBK, rats inhaled 600ppm for 212 hours or 1300ppm for 6 hours per day, 5days per week up to 17 weeks. For HD, 350 to 520mg/kg per day were given orally or 230 to 340mg/kg per day were injected sc 5 days per week for 13 weeks. Clinical observations were recorded. Tissue samples were perfused and examined. Rats breathing 1300ppm MBK exhibited narcosis. Animals receiving HD had hair discoloration. Exposed animals did not gain weight as quickly as untreated controls. Neuropathic symptoms were the same for all compounds. Giant axonal degeneration occurred at progressively ascending sites in peripheral nerve trunks, accompanied by slowly progressive distal, symmetrical neuropathy. Perivascular endoneural edema was seen prior to axonal swellings, which appeared on the proximal sides of multiple paranodes, then at facing paranodes, and internodal loci. Numerous Schwann cells were found on the denuded areas. The authors conclude that giant axonal swelling at the proximal sides of nodes of Ranvier suggests that the node is vulnerable to the action of neurotoxic compounds.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Animal-studies; Inhalants; Neurotoxins; Exposure-levels; Breathing-atmospheres; Biological-effects; Physiological-testing
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
110-54-3; 591-78-6; 110-13-4
Neurotoxic Disorders; Neurotoxic-effects
Journal of Neuropathology and Experimental Neurology
Yeshiva University, New York, New York