Acta Neuropathologica

, Volume 64, Issue 2, pp 99–107 | Cite as

A study of experimental cyanide encephalopathy in the acute phase —Physiological and neuropathological correlation

  • N. Funata
  • S. -Y. Song
  • R. Okeda
  • M. Funata
  • F. Higashino
Original Works


A study was performed to elucidate the significance of various physiological factors contributing to the pathogenesis of experimental cyanide encephalopathy, such as the systemic arterial blood pressure, venous pressure, common carotid blood flow and local blood flow of the cerebral grey and white matters, and blood gas including pH. The histology and topography of the brain damage was also analysed. Twenty-one cats were divided into four groups. The animals in groups 1, 2 and 3 were subjected to continuous infusion of 0.2% sodium cyanide solution and to the ensuing hypotension below 100 mm Hg by administering a ganglion-blocking drug and by respiratory arrest. Severe damage developed in the deep cerebral white matter, corpus callosum, pallidum and substantia nigra, but the damage of the cerebral cortex and hippocampus was not remarkable. The animals in group 4 that were subjected to cyanide infusion without significant hypotension (above 100 mm Hg), but to the same degree of acidosis as that of the the other groups, had similar morphological changes, but to a lesser degree. On the basis of our physiological and morphological findings, we speculated that the pathophysiological factors of tissue hypoxia and subsequent hypotension operated in cyanide leucoencephalopathy. The topographic selectivity seemed to be related to the characteristic cerebral vascular system, and the severity of the white matter lesions was related to the intensity of both hypoxia and hypotension during cyanide infusion, but not to the extent of acidosis, total dose of cyanide or duration of its infusion per se.

Key words

Cyanide encephalopathy Selective white matter lesion Cerebral local blood flow 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams JH, Brierley JB, Conner RCA, Triep CS (1966) The effects of systemic hypotension upon the human brain. Brain 89:235–268Google Scholar
  2. 2.
    Bass NH (1968) Pathogenesis of myelin lesions in experimental cyanide encephalopathy. A microchemical study. Neurology 18:167–177Google Scholar
  3. 3.
    Brierley JB, Brown AW, Calverley J (1976) Cyanide intoxication in the rat; physiological and neuropathological aspects. J Neurol Neurosurg Psychiatry 39:129–140Google Scholar
  4. 4.
    Brierley JB, Prior PF, Calverley J, Brown AW (1977) Cyanide intoxication inMacaca mulatta. Physiological and neuropathological aspects. J Neurol Sci 31:133–157Google Scholar
  5. 5.
    Eunata N, Okeda R, Takano T, Miyazaki Y, Higashino F, Yokoyama K, Manabe M (1982) Electron-microscopic observations of experimental carbon monoxide encephalopathy in the acute phase. Acta Pathol Jpn 32:219–229Google Scholar
  6. 6.
    Ginsberg MD, Myers RE (1974) Experimental carbon monoxide encephalopathy in the primate. I. Physiologic and metabolic aspects. Arch Neurol 30:202–208Google Scholar
  7. 7.
    Ginsberg MD, Myers RE, McDonagh BF (1974) Experimental carbon monoxide encephalopathy in the primate. II. Clinical aspects, neuropathology, and physiologic correlation. Arch Neurol 30:209–216Google Scholar
  8. 8.
    Haymaker W, Ginzler AM, Ferguson RL (1952) Residual neuropathological effects of cyanide poisoning. A study of the central nervous system of 23 dogs exposed to cyanide compounds. Milit Surg 111:231–246Google Scholar
  9. 9.
    Hieks SP (1950) Brain metabolism in vivo. I. The distribution of lesions caused by cyanide poisoning, insulin hypoglycemia, asphyxia in nitrogen and fluoroacetate poisoning in rats. Arch Pathol 49:111–137Google Scholar
  10. 10.
    Hirano A, Levine S, Zimmerman HM (1967) Experimental cyanide encephalopathy: Electron-microscopic observations of early lesions in white matter. J Neuropathol Exp Neurol 26:200–213Google Scholar
  11. 11.
    Hirner A (1969) Elektronenmikroskopische Untersuchungen zur formalen Genese der Balkenläsionen nach experimenteller Cyanvergiftung. Acta Neuropathol (Berl) 13:350–368Google Scholar
  12. 12.
    Hurst EW (1940) Experimental demyelination of the central nervous system. 1. Encephalopathy produced by potassium cyanide. Aust J Exp Biol Med Sci 18:201–223Google Scholar
  13. 13.
    Hurst EW (1942) Experimental demyelination of the central nervous system. 3. Poisoning with potassium cyanide, sodium azide, hydroxylamine, narcotics, carbon monoxide, etc., with some consideration of bilateral necrosis occurring in the basal nuclei. Aust J Exp Biol Med Sci 20:297–312Google Scholar
  14. 14.
    Kalimo H, Rehncrona S, Söderfeldt B, Olsson Y, Siesjö BK (1981) Brain lactic acidosis and ischemic cell damage. 2. Histopathology. J Cereb Blood Flow Metabol 1:313–327Google Scholar
  15. 15.
    Kennedy C, Sakurada O, Shinohara M, Jehle J, Sokoloff L (1978) Local cerebral glucose utilization in the normal conscious macaque monkey. Ann Neurol 4:293–301Google Scholar
  16. 16.
    Klimmek R, Roddewig C, Fladerer H, Weger N (1982) Cerebral blood flow, circulation and blood homeostasis of dogs during slow cyanide poisoning and after treatment. Arch Toxicol 50:65–76Google Scholar
  17. 17.
    Kogure K, Busto R, Matsumoto A, Scheinberg P, Reimuth OM (1975) Effect of hyperventilation on dynamics of cerebral energy metabolism. Am J Physiol 228:1862–1867Google Scholar
  18. 18.
    Lessell S, Kuwabara T (1974) Fine structure of experimental cyanide optic neuropathy. Invest Ophthalmol 13:748–756Google Scholar
  19. 19.
    Levine S, Stypulkowski W (1959) Experimental cyanide encephalopathy. Arch Pathol 67:306–323Google Scholar
  20. 20.
    Levine S, Wenk EJ (1959) Cyanide encephalopathy produced by intravenous route. J Nerv Ment Dis 129:302–305Google Scholar
  21. 21.
    Levine S (1967) Experimental cyanide encephalopathy. Gradients of susceptibility in the corpus callosum. J Neuropathol Exp Neurol 26:214–222Google Scholar
  22. 22.
    Lumsden CE (1950) Cyanide leucoencephalopathy in rats and observations on the vascular and ferment hypothesis of demyelination disease. J Neurol Neurosurg Psychiatry 13:1–15Google Scholar
  23. 23.
    Myers RE (1979) A unitary theory of causation of anoxic and hypoxic brain pathology. In: Fahn S, Davis JN, Rowland LP (eds) Advances in neurology, vol 26. Raven Press, New York, pp 195–213Google Scholar
  24. 24.
    Naganuma M (1975) Electron-microscopic studies on the cerebral lesions of rats in experimental chronic cyanide poisoning (in Japanese). Psychiat Neurol Jpn 77:219–243Google Scholar
  25. 25.
    Okeda R, Funata N, Takano T, Miyazaki Y, Higashino F, Yokoyama K, Manabe M (1981) The pathogenesis and morphological correlation. Acta Neuropathol (Berl) 54:1–10Google Scholar
  26. 26.
    Okeda R, Funata N, Song S.-Y., Higashino F, Takano T, Yokoyama K (1982) Comparative study on pathogenesis of selective cerebral lesions in carbon monoxide poisoning and nitrogen hypoxia in cats. Acta Neuropathol (Berl) 56:265–272Google Scholar
  27. 27.
    Palay SL, Chan-Palay V (1974) Cerebellar cortex: Cytology and organization. Springer, Berlin Heidelberg New YorkGoogle Scholar
  28. 28.
    Preziosi T, Lindenberg R, Levy D, Christenson M (1970) An experimental investigation in animals of the functional and morphologic effects of single and repeated exposures to high and low concentration of carbon monoxide. Ann NY Acad Sci 174:369–384Google Scholar
  29. 29.
    Song S-Y, Okeda R, Funata N, Higashino F (1983) An experimental study of the pathogenesis of the selective lesion of the globus pallidus in acute carbon monoxide poisoning with special reference to the chronologic change in the cerebral local flow. Acta Neuropathol (Berl) 61:232–238Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • N. Funata
    • 1
  • S. -Y. Song
    • 1
  • R. Okeda
    • 1
  • M. Funata
    • 1
  • F. Higashino
    • 2
  1. 1.Dept. of Pathology, Medical Research InstituteTokyo Medical and Dental UniversityBunkyo-ku, TokyoJapan
  2. 2.Dept. of Mechanical Engineering, Faculty of EngineeringTokyo Noko UniversityTokyoJapan

Personalised recommendations