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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Behan, W. M. H., Maia, M.: Strumpell's familial spastic paraplegia: genetics and neuropathology. J. Neurol. Neurosurg. Psychiatry37, 9–20 (1974)
Cook, D. R., Wisniewski, M. H.: The role of oligodendroglia and astroglia in Wallerian degeneration of the optic nerve. Brain Res.101, 191–206 (1973)
Egashira, Y., Matsuyama, H., Fujisawa, K.: Light and Electron microscopical findings in the peripheral nerves of the puppies chronically intoxicated with chinoform. General Meeting of the SMON Research Commitee, Zenkyoren Building, Tokyo, March 24, 1977
Hess, R., Thomann, P., Krinke, G.: The assessment of neurotoxicity in laboratory animals. Proc. of the 1st Internatl. Congr. on Toxicology: Toxicology as a predictive science. Plaa, G. L., Duncan, W. A. M. (eds.), pp. 245–268. New York, San Francisco, London: Academic Press 1978
Heywood, R., Chesterman, H., Worden, A. N.: The oral toxicity of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in Beagle dogs. Toxicology6, 41–46 (1976)
Kono, R.: Subacute myelo-optico-neuropathy, a new neurological disease prevailing in Japan. Jpn. Med. Sci. Biol.24, 195–216 (1971)
Krinke, G., Pericin, C., Thomann, P., Hess, R.: Toxic Encephalopathy with Hippocampal Lesions. Zentralbl. Veterinaermed. [A]25, 277–296 (1978)
Lampert, P. W.: A comparative electron microscopic study of reactive, degenerating, regenerating and dystrophic axons. J. Neuropathol. Exp. Neurol.26, 345–368 (1967)
Schaumburg, H. H., Spencer, P. S.: Central and peripheral nervous system degeneration produced by pure n-Hexane; an experimental study. Brain99, 183–192 (1976)
Schaumburg, H. H., Spencer, P. S.: Toxic neuropathies. Neurology (Minneap.)29, 429–431 (1979)
Schmid, K., Krike, G., Früh, F., Keberle, H.: Studies of the distribution and excretion of clioquinol in the animal. Arzneim. Forsch.23, 1560–1566 (1973)
Shiraki, H.: Neuropathology of subacute myelooptico neuropathy in humans with special reference to experimental whole body autoradiographic studies using labelled quinoform compounds. In: Neurotoxicology, Vol. 1. Roizin, L., Shiraki, H., Grcevic, N. (eds.), pp. 327–344. New York: Raven Press 1977
Spencer, P. S., Schaumburg, H. H.: Ultrastructural studies of the dying-back process IV. Differential vulnerability of PNS and CNS fibres in experimental central-peripheral distal axonopathies. J. Neuropathol. Exp. Neurol.36, 300–320 (1977)
Spencer, P. S., Schaumburg, H. H.: Pathobiology of neurotoxic axonal degeneration. In: Physiology and pathobiology of axons. Waxman, S. (ed.), pp. 265–282. New York: Raven Press 1978
Tateishi, J., Kuroda, S., Ikeda, H., Otsuki, S.: Experimental subacute myeloopticoneuropathy. In: Neurotoxicology, Vol. 1, Roizin, L., Shiraki, H., Grcevic, N. (eds.), pp. 345–351. New York: Raven Press 1977
Thomann, P., Koella, W. P., Krinke, G., Petermann, H., Zak, F., Hess, R.: The assessment of peripheral neurotoxicity in dogs: Comparative studies with acrylamide and clioquinol. Agents Actions4, 47–53 (1974)
Thomas, P. K.: pers. commun. (1979)
Worden, A. N., Heywood, R., Prentice, D. E., Chesterman, H., Skerrett, K., Thomann, P.: Clioquinol toxicity in the dog. Toxicology9, 227–238 (1978)
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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