Distal terminal axonopathy produced by 2,4-dithiobiuret: effects of long-term intoxication in rats.
It has been well established that 2,4-dithiobiuret (DTB) intoxication in rats produces a rapidly progressive hindlimb paralysis within days. The cause of this has, until recently, been explained on the basis of a physiological abnormality that involves a prejunctional impairment in the neuromuscular transmission alone. The morphological correlate of the electrophysiological abnormalities has now been provided. This study describes the sequential morphological alterations resulting from a chronic long-term DTB intoxication (1 mg/kg per day, IP) in the rat nervous system up to 48 days. The findings indicate that DTB neurotoxicity evolves as a central peripheral distal axonopathy initially affecting the motor nerve terminals which show accumulation of interconnecting branched tubulovesicular profiles. With continued exposure, nerve terminal swelling and degeneration took place. Similar pathological changes in distal axons were observed progressively involving the small intramuscular nerve bundles close to the nerve terminals. Central nervous system axons in the long descending tracts of spinal cord and the cerebellar vermis showed similar changes but to a lesser extent in later stage of intoxication.
Sahenk
Z
Z
Department of Neurology, Ohio State University, Columbus 43210.
D000818:Animals; D001369:Axons / Q000187:drug effects*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009132:Muscles / Q000294:innervation / Q000473:pathology; D009410:Nerve Degeneration / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D010543:Peroneal Nerve / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000648:ultrastructure; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity
D013890:Thiourea; C007540:2,4-dithiobiuret