Ultrastructural studies of the dying-back process. V. axonal neurofilaments accumulate at sites of 2,5-hexanedione application: evidence for nerve fibre dysfunction in experimental hexacarbon neuropathy.
Politis MJ; Pellegrino RG; Spencer PS
J Neurocytol 1980 Aug; 9(4):505-516
The production of distal axonopathy by the direct toxic effects of 2,5-hexanedione (110134) (25HD) on nerve fibers was assessed in Sprague-Dawley-rats. Sciatic nerves of the test animals were exposed and treated with 25HD, 2,4-hexanedione (3002242) (24HD), 1,6- hexanediol (629118) (16HDiol), saline, or an aqueous solution of hydrochloric-acid (7647010) (HCl) daily for periods of up to 8 days with and without oral 25HD treatment for 8 days prior to surgery. Nerves were examined by electron microscopy at times between 6 hours and 16 days post treatment. Oral exposure to 25HD in the drinking water and the direct application of 25HD to the sciatic nerve produced unilateral hindlimb weakness concomitant with nerve fiber breakdown at the site of application and diffuse Wallerian degeneration of the distal zone. Light microscopy revealed swollen myelinated and demyelinated axons with a similar appearance to the giant axonal swellings characteristic of systemic hexacarbon neuropathy. Electron microscopic examination at 4 and 16 days post treatment showed swollen demyelinated axons filled with 10 nanometer neurofilaments and containing scattered clusters of microtubules and Schwann cell necrosis. No qualitative differences were determined for oral versus direct nerve exposure to the agent, but animals exposed to 25HD in the drinking water and by direct nerve application had a higher incidence of axonal swellings. Treatment of the nerve fibers with 24HD produced a nonspecific breakdown of nerve tissue and Schwann cells without any significant effect on the axonal distribution of neurofilaments and microtubules. Treatment with 16HDiol was without effect. The authors conclude that 25HD can induce the formation of giant axonal swellings through direct toxic action and that the Schwann cell changes observed after application of 25HD or 24HD are nonspecific and not related to axonal swelling.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Microscopic-analysis; Histopathology; Organic-solvents; Nerve-damage; Peripheral-nervous-system
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
110-13-4; 3002-24-2; 629-11-8; 7647-01-0
Neurotoxic Disorders; Neurotoxic-effects
Journal of Neurocytology
Yeshiva University, New York, New York