Summary
Ouabain, a specific inhibitor of active cation transport across cell membrane, was applied topically to brain surface of cats. The cerebral cortex to which 10−3 M ouabain was applied showed a spongy state, which was ultrastructurally revealed to be swelling of the neuronal cell processes, especially of dendrites. Astrocytes did not show swelling even in the most severely affected lesions. There was a marked increase in sodium with a slight increase of water in the most severely affected lesions. There was a marked increase in sodium with a slight increase of water in the cortex treated with 10−3 M ouabain. No evidence of increased vascular permeability was noted in the cortex, morphologically or biochemically. Electron microscopic cytochemistry to detect the sodium ion revealed that the increased sodium in the cortex accumulated in the swollen neuronal cell processes.
It is speculated that neuronal rather than astrocytic elements might be highly dependent upon active cation transport, and that intracellular oedema in the brain tissue responsible for impairment of active cation transport might be related primarily to neuronal elements.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ayala, G. F., Lin, S., Vascontetto, C.: Penicillin as epileptogenic agent: Its effect on an isolated neuron. Science167, 1257 (1970)
Bakay, L., Lee, J. C.: The effect of acute hypoxia and hypercapnia on the ultrastructure of the central nervous system. Brain91, 697–706 (1968)
Cornog, G. L., Gonatas, N. K., Feierman, J. R.: Effects of intracerebral injection of ouabain on the fine structure of rat cerebral cortex. Amer. J. Path.51, 573–590 (1967)
Cummins, J., Hydén, H.: Adenosine triphosphate levels and adenosine triphosphatases in neurons, glia and neuronal membranes of the vestibular nucleus. Biochim. biophys. Acta (Amst.)60, 271–283 (1962)
Davis, B. J.: Disc electrophoresis. II. Method and application on human serum protein. Ann. N.Y. Acad. Sci.121, 404–427 (1964)
Elliot, K. A. C., Jasper, H.: Measurement of experimentally induced brain swelling and shrinkage. Amer. J. Physiol.157, 122–129 (1949)
Hartmann, J. F.: High sodium content of cortical astrocytes. Arch. Neurol. (Chic.)15, 633–642 (1966)
Hess, H. H., Pope, A.: Effects of metal cations on adenosine triphosphatase activity of rat brain. Fed. Proc.16, 196 (1957)
Hess, H. H., Schneider, G., Warnock, M., Pope, A.: Lack of effect of Na plus K on Mg-stimulated ATP phosphohydrolase activity of human astrocytomas. Fed. Proc.22, 333 (1963)
Hirano, A., Levin, S., Zimmerman, H. M.: Experimental cyanide encephalopathy: Electron microscopic observations of early lesions in white matter. J. Neuropath. exp. Neurol.26, 200–213 (1967)
Ishii, S.: Brain swelling. Studies of structural, physiological and biochemical alterations. In: Head Injury (eds. W. F. Caveness, A. E. Walker), pp. 276–299. Philadelphia-Toronto: Lippincott Co. 1966
Katzman, R.: Electrolyte distribution in mammalian central nervous system. Are glia high sodium cells? Neurology (Minneap.)11, 27–36 (1961)
Klatzo, I.: Neuropathological aspects of brain edema. J. Neuropath. exp. Neurol.26, 1–14 (1967)
Komnick, H.: Elektronenmikroskopische Lokalisation von Na+ und Cl− in Zellen und Geweben. Protoplasma (Wien)55, 414–418 (1962)
Krigman, M. R., Buck, E. L.: Ouabain encephalopathy: A temporal study of histological, electrolyte, and Na−K stimulated adenosine triphosphatase changes. J. Neuropath. exp. Neurol.29, 151–152 (1970)
Levin, E., Hess, H. H.: Intralaminar distribution of Na-K-adenosine triphosphatase in rat cortex. J. Neurochem.11, 473–481 (1964)
Millonig, G.: Advantages of a phosphate buffer for osmium tetroxide solution in fixation. J. appl. Physiol.32, 1637 (1961)
Miyagishi, T., Suwa, N.: Electron microscopic studies on the cerebral lesions of rats in experimental carbon-monoxide poisoning. Acta neuropath. (Berl.)14, 118–125 (1969)
Okada, K., Ayala, G. F., Sung, J. H.: Ultrastructure of penicillin-induced epileptogenic lesion of the cerebral cortex in cats. J. Neuropath. exp. Neurol.30, 337–353 (1971)
Ornstein, L.: Disc electrophoresis. I. Background and theory. Ann. N.Y. Acad. Sci.121, 321–349 (1964)
Ozawa, K., Itada, N., Kuno, S., Handa, H., Araki, C.: Biochemical studies on brain swelling. I. Changes in respiratory control, 2,4-dinitrophenol-induced ATPase activity and phosphorylation. Correlation between brain swelling and mitochondrial function. Folia psychiat. neurol. jap.20, 57–72 (1966)
Post, R. L.: Relationship of an ATPase in human erythrocyte membranes to the active transport of sodium and potassium. Fed. Proc.18, 121 (1959)
Reulen, H. J., Baethmann, A.: Das Dinitrophenol-Ödem. Ein Modell zur Pathophysiologie des Hirnödems. Klin. Wschr.45, 149–154 (1967)
Skou, J. C.: The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim. biophys. Acta (Amst.)23, 394–401 (1957)
Solheid, C., Palladini, G.: Morphological changes induced by ouabain in normal and neoplastic human glia in monolayer culture. Acta neuropath. (Berl.)28, 253–260 (1974)
Tanimura, K.: Biochemical study of brain edema. III. Effects of Na-K-activated ATPase inhibitor on cat's cerebral cortex in vivo. Brain Nerve21, 467–474 (1969)
Towfighi, J., Gonatas, N. K.: Effect of intracerebral injection of ouabain in adult and developing rats. An ultrastructural and autoradiographic study. Lab. Invest.28, 170–180 (1973)
Wolff, J. R., Schieweck, Ch., Emmenegger, H., Meier-Ruge, W.: Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine. Acta neuropath. (Berl.)31, 45–58 (1975)
Zadunaisky, J. A., Wald, F., DeRobertis, E. D. P.: Osmotic behavior and ultrastructural modifications in isolated frog brains. Exp. Neurol.8, 290–309 (1963)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tanaka, R., Tanimura, K. & Ueki, K. Ultrastructural and biochemical studies on ouabain-induced oedematous brain. Acta Neuropathol 37, 95–100 (1977). https://doi.org/10.1007/BF00692054
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00692054