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Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog

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Summary

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 animals 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.

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Krinke, G., Schaumburg, H.H., Spencer, P.S. et al. Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog. Acta Neuropathol 47, 213–221 (1979). https://doi.org/10.1007/BF00690549

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  • DOI: https://doi.org/10.1007/BF00690549

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