Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog.
The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animal were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves.
D000818:Animals; D001369:Axons; D001921:Brain / Q000648:ultrastructure; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D007464:Clioquinol; D004285:Dogs; D007659:Ketones / Q000031:analogs & derivatives; D008742:Methyl n-Butyl Ketone / Q000031:analogs & derivatives; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000473:pathology; D010525:Peripheral Nerves / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology
D007659:Ketones; D008742:Methyl n-Butyl Ketone; D007464:Clioquinol