Summary
Twenty nine out of 42 sheep were given copper sulphate daily by mouth and the remaining 13 were undosed controls. Nine of the dosed animals were killed before the haemolytic crisis of chronic copper poisoning developed, 11 sheep died during haemolysis and 9 died subsequent to haemolysis. The central nervous system was fixed either by perfusion or immersion. Light microscopical studies showed that astrocytic changes were present in the haemolytic and post haemolytic groups and that in brain tissue fixed by immersion the volume of astrocytic nuclei was significantly greater than that of controls. Vacuolation of white matter was seen as a terminal phenomenon in some but not all the affected sheep. Ultrastructural studies showed that most of the vacuoles associated with nerve fibres were in the outer tongue of oligodendrocyte cytoplasm. The swollen astrocytes contained more glycogen, mitochondria and endoplasmic reticulum than normal and the last was often expanded into vacuoles. Serum ure levels were high in animals during the haemolytic and post haemolytic phases. One animal that died during haemolysis and two that died after haemolysis had raised plasma ammonia levels. It seems possible that the changes that occur in the brain of animals in chronic chopper poisoning are due to the effects of altered metabolic processes on glial transport mechanisms.
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Adachi, M., Torri, J., Wellmann, K. F., Volk, B. W.: Early central nervous system lesions in experimental hypercholesterolemia in normal and subdiabetic rabbits. Acta neuropath. (Berl.)22, 58–67 (1972)
Adachi, M., Wallace, B. J., Schneck, L., Volk, B. W.: Fine structure of spongy degeneration of the central nervous system (Van Bogaert and Bertrand type). J. Neuropath. exp. Neurol.25, 598–616 (1968)
Adams, R. D., Foley, J. M.: Neurological complications of liver disease. Res. Publ. Ass. nerv. ment. Dis.32, 198–237 (1953)
Adornato, B., Lampert, P.: Status spongiosus of nervous tissue. Electron microscopic studies. Acta neuropath. (Berl.)19, 271–289 (1971)
Aleu, F. P., Katzman, R., Terry, R. D.: Fine structure and electrolyte analysis of cerebral edema induced by Alkyl tin intoxication. J. Neuropath. exp. Neurol.22, 403–413 (1963)
Anon: The astrocyte in liver disease. Lancet1971II, 1189–1190
Blakemore, W. F.: The ultrastructural appearance of astrocytes following thermal lesions of the rat cortex. J. neurol. Sci.12, 319–332 (1971)
Blakemore, W. F.: Observations on oligodendrocyte degeneration, the resolution of status spongiosus and remyelination in cuprizone intoxation in mice. J. neurocytol.1, 413–426 (1972)
Blakemore, W. F., Palmer, A. C., Noel, P. R. B.: Ultrastructural changes in isoniazid-induced brain oedema in the dog. J. neurocytol.1, 263–278 (1972)
Bowler, K., Duncan, C. J.: The effect of copper on membrane enzymes. Biochim. biophys. Acta (Amst.)196, 116–119 (1970)
Cavanagh, J. B.: Cellular abnormalities in the brain in chronic liver disease. Ann. Rev. Scientific basis of Med. 238–247 (1972)
Cavanagh, J. B., Kyu, M. H.: Type II Alzheimer change experimentally produced in astrocytes in the rat. J. neurol. Sci.12, 63–75 (1971)
Cordy, D. R., Richards, W. P. C., Stormont, C.: Hereditary neuraxial edema in Hereford calves. Path. vet.6, 487–501 (1969)
Doherty, P. C., Barlow, R. M., Angus, K. W.: Spongy changes in the brains of sheep poisoned by excess dietary copper. Res. Vet. Sci.10, 303–304 (1969)
Epstein, P. S., McIlwain, H.: Actions of cupric salts on isolated cerebral tissue. Proc. roy. Soc. B116, 295–302 (1966)
Faweett, J. K., Scott, J. E.: A rapid and precise method for the determination of urea. J. clin. Path.13, 156–159 (1960)
Fenton, J. C. B.: The estimation of plasma ammonia by ionexchange. Clin. chim. Acta7, 163–175 (1962)
Gonatas, N. K.: Comparative study of status spongiosus in human and experimental toxic encephalopathies. Proc. VI. Int. Cong. Neuropath., Paris, pp. 49–59. Paris: Masson et Cie. 1970
Gopinath, C., Hall, G. A., Howell, J. McC.: The effect of chronic copper poisoning on the kidneys of sheep. Res. Vet. Sci.16, 57–69 (1974)
Hall, G. A., Reid, I. M.: Hexachlorophane toxicity in sheep. Lancet1972 II, 1251
Hooper, P. T.: Spongy degeneration in the brain in relation to hepatic disease and ammonia toxicity in domestic animals. Vet. Rec.90, 37–38 (1972)
Hooper, P. T., Best, S. M., Murray, D. R.: Hyperammonaemia and spongy degeneration of the brain in sheep affected with hepatic necrosis. Res. Vet. Sci.16, 216–222 (1974)
Ishmael, J., Gopinath, C., Howell, J. McC.: Experimental chronic copper toxicity in sheep. Res. Vet. Sci.12, 358–366 (1971)
Ishmael, J., Gopinath, C., Howell, J. McC.: Experimental chronic copper toxicity in sheep. Biochemical and haematological studies during the development of lesions in the liver. Res. Vet. Sci.13, 22–29 (1972)
Kimbrough, R. D., Gaines, T. B.: Hexachlorophene effects on the rat brain. Arch. environm. Hlth.23, 114–118 (1971)
Knutson, J., Baker, A. B.: The central nervous system in uraemia. Arch. Neurol. Psychiat. (Chic.)54, 130–140 (1945)
Kuffler, S. W., Nicholls, J. G.: The physiology of neuroglial cells. Ergebn. Physiol.57, 1–90 (1966)
Lampert, P. W., Schochet, S. S.: Electron microscopic observations on experimental spongy degeneration of the cerebellar white matter. J. Neuropath. exp. Neurol.27, 210–220 (1968)
Martinez, A.: Electron microscopy in human hepatic encephalopathy. Acta neuropath. (Berl.)11, 82–86 (1968)
Morgan, K. T.: Chronic copper toxicity of sheep: An ultrastructural study of spongiform leucoencephalopathy. Res. Vet. Sci.15, 88–95 (1973)
Nara, E., Yasunoku, K. T.: Some recent advances in the field of amine oxidases. In the biochemistry of copper. J. Peisach, P. Aisen, and W. E. Blumberg (Eds.). New York: Academic Press 1966
Olsen, S.: The brain in uraemia. Acta psychiat. neurol. scand.36, Suppl. 156 (1961)
Palmer, A. C., Noel, P. R. B.: Neuropathological effects of prolonged administration of some hydrazine monoamine oxidase inhibitors in dogs. J. Path. Bact.86, 463–476 (1963)
Peters, R. A., Shorthouse, M., Walshe, J. M.: Studies on the toxicity of copper. II. The behaviour of microsomal membrane ATPase of the pigeon's brain tissue to copper and some other metallic substance. Proc. roy. Soc. B166, 285–294 (1966)
Ross, D. B.: The diagnosis, prevention and treatment of chronic copper poisoning in housed lambs. Brit. vet. J.122, 279–284 (1966)
Singer, R. H., McCarty, R. T.: Pathologic changes resulting from acute ammonium salt poisoning in sheep. Amer. J. vet. Res.32, 1239–1246 (1971)
Suzuki, K., Kikkawa, Y.: Status spongiosus of CNS and hepatic changes induced by Cuprizone (Biscyclohexanone Oxaldihydrazone). Amer. J. Path.54, 307–321 (1969)
Todd, J. R.: Chronic copper toxicity of ruminants. Proc. Nutr. Soc.28, 189–198 (1969)
Todd, J. R., Thompson, R. H.: Studies on chronic copper poisoning. II. Biochemical studies on the blood of sheep during the haemolytic crisis. Brit. vet. J.119, 161–173 (1963)
Victor, M., Adams, R. D., Cole, M.: The acquired (non-Wilsonian) type of chronic hepatocerebral degeneration. Medicine (Baltimore)44, 345–396 (1965)
Vogel, F. S., Evans, J. W.: Morphologic laterations produced by copper in neural tissues with consideration to the role of the metal in the pathogenesis of Wilson's disease. J. exp. Med.113, 997–1004 (1961)
Wills, M. R.: The biochemical consequences of chronic renal failure. London, Oxford, New York: Harvey, Miller, Metcalf 1971
Zamora, A. J., Cavanagh, J. B., Kyu, M. H.: Ultrastructural responses of the astrocytes to portojcaval anastomosis in the rat. J. neurol. Sci.18, 25–45 (1973)
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Howell, J.M., Blakemore, W.F., Gopinath, C. et al. Chronic copper poisoning and changes in the central nervous system of sheep. Acta Neuropathol 29, 9–24 (1974). https://doi.org/10.1007/BF00684387
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DOI: https://doi.org/10.1007/BF00684387