Susceptibility to Spreading Depression and Anoxia: Regional Differences and Drug Control

  • Jan Bureš
  • Olga Burešová
Part of the Advances in Behavioral Biology book series (ABBI, volume 35)


Anoxic depolarization (AD) of cerebral cortex, a negative slow potential developing several minutes after interruption of cerebral blood flow and cessation of EEG activity, was described forty years ago by Leao (1947). This important paper followed shortly after discovery of spreading depression (SD) of EEG activity (Leao 1944) and demonstrated for the first time that the wavefront of reduced EEG amplitude propagating at a rate of 3 mm/min across the cortical surface of the rabbit brain is accompanied by a negative slow potential. It pointed out the essential similarity of the DC shifts occurring during SD and AD in the rabbit cerebral cortex but also showed important differences between the two phenomena: whereas during SD the negative slow potential coincides with the suppression of EEG activity, AD starts several minutes after complete disappearance of EEG during anoxia. This finding disproved the possibility that SD is a vascular phenomenon due to a propagating wave of vasoconstriction and oriented further research into the nature of both phenomena toward the underlying electrolyte shifts.


Cerebral Cortex Olfactory Bulb Cortical Spreading Depression Spreading Depression Ischemic Brain Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amemori, T., and Bures, J., 1986, Terminal anoxic depolarization proceeds more slowly in the olfactory bulb than in the cerebral cortex of rats, Neurosci. Lett., 71: 323–328.CrossRefGoogle Scholar
  2. Amemori, T., Gorelova, N. A., and Bures, J., 1987, Spreading depression in the olfactory bulb of rats: reliable initiation and boundaries of propagation, Neuroscience, 22: 29–36.CrossRefGoogle Scholar
  3. Aquino-Cias, J., and Bures, J., 1966, The effect of thalamic spreading depression on the epileptic discharge in rats, in: “Comparative and Cellular Pathophysiology of Epilepsy, Z. Servit, ed., Excerpta Medica, Amsterdam, pp. 258–289.Google Scholar
  4. Astrup, J., Blennow, G., and Nilsson, B., 1980, Effect of reduced cerebral blood flow upon EEG pattern, cerebral extra-cellular potassium, and energy metabolism in the rat cortex during bicuculline-induced seizures, Brain Res., 177: 115–126.CrossRefGoogle Scholar
  5. Benešová, O., Bureš, J., and Burešová, O., 1957, Die Wirkung des Chlorpromazins und der Glykämie auf das elektrophysiologisch kontrollierte überleben der Hirnrinde bei verschiede-nen Körpertemperaturen, Arch. Exp. Path. Pharmak., 231: 550–561.CrossRefGoogle Scholar
  6. Brinley, F. J., Kandel, E. R., and Marshall, W. H., 1960, Potassium outflux from rabbit cortex during spreading depression, J. Neurophysiol., 23: 246–256.Google Scholar
  7. Bureš, J., 1957a, Ontogenetic development of steady potential differences in cerebral cortex in animals, Electroenceph. clin. Neurophysiol., 9: 121–130.CrossRefGoogle Scholar
  8. Bures, J., 1957b, The effect of anoxia and asphyxia on spreading EEG depression, Physiol. bohemoslov., 6: 444–453.Google Scholar
  9. Bureš, J., 1960, Block of Leao’s spreading cortical depression by bivalent cations, Physiol. bohemoslov., 9: 202–209.Google Scholar
  10. Bureš, J., and Burešová, O., 1957, Die anoxische Terminaldepolarisation als Indicator der Vulnerabilität der Grosshirnrinde bei Anoxie und Ischämie, Pflügers Arch., 264: 325–334.CrossRefGoogle Scholar
  11. Bureš, J., and Burešová, O., 1960, Activation of latent foci of spreading cortical depression in rats, J. Neurophysiol., 23: 225–236.Google Scholar
  12. Bureš, J., and Burešová, O., 1981, Cerebral /K+/ increase as an index of the differential susceptibility oY brain structures to terminal anoxia and electroconvulsive shock, J. Neurobiol., 12: 211–220.CrossRefGoogle Scholar
  13. Bureš, J., Burešová, O., and Krivânek, J., 1974, “The Mechanism and Applications of Leao’s Spreading Depression of Electroencephalographic Activity”, Academic Press, New York.Google Scholar
  14. Bure, J., Burešová, O., and Zacharovš, D., 1957, Effect of changes in body temperature on spreading EEG depression, Physiol. bohemoslov., 6: 454–461.Google Scholar
  15. Bureš, J., and Krivânek, J., 1960, Ionic movements in the brain as studied with the aid of washing the cortical surface with an epidural cannula, Physiol. bohemoslov., 9: 488–493.Google Scholar
  16. Curtis, D. R., and Watkins, J. C., 1963, Acidic amino acids with strong excitatory actions on mammalian neurones, J. Physiol., 166: 1–14.Google Scholar
  17. DeLuca, B., and Bure, J., 1977, Development of cortical spreading depression and of its transition to the caudate nucleus in rats, Develop. Psychobiol., 19: 289–297.CrossRefGoogle Scholar
  18. Duffy, T. E., Kohle, S. J., and Vannucci, R. C., 1975, Carbohydrate and energy metabolism in perinatal rat brain: relation to survival in anoxia, J. Neurochem., 24: 271–276.CrossRefGoogle Scholar
  19. Gardner-Medwin, A. R., 1981, Possible roles of vertebrate neuro-glia in potassium dynamics, spreading depression and migraine, J. exp. Biol., 95: 111–127.Google Scholar
  20. Gorelova, N. A., Koroleva, V. I., Amemori, T., Pavlík, V., and Bure, J., 1987, Ketamine blockade of cortical spreading depression in rats, Electroenceph. clin. Neurophysiol., 66: 440–447.CrossRefGoogle Scholar
  21. Grafstein, B., 1956, Mechanism of spreading cortical depression, J. Neurophysiol., 19: 154–171.Google Scholar
  22. Hagberg, H., Lehmann, A., Sandberg, M., Nyström, B., Jacobson, I., and Hamberger, A., 1985, Ischemia-induced shift of inhibitory and excitatory amino acids from intra-to extracellular compartments, J. Cereb. Blood Flow Metabol., 5: 413–419.CrossRefGoogle Scholar
  23. Hägerdal, M., Harp, J. R., Nilsson, L., and Siesjö, B. K., 1975, The effect of induced hypothermia upon oxygen consumption in the rat brain, J. Neurochem., 24: 311–316.CrossRefGoogle Scholar
  24. Hammer, R. P., Jr., and Herkenham, M., 1983, Altered metabolic activity in the cerebral cortex of rats exposed to ketamine, J. Comp. Neurol., 220: 390–404.CrossRefGoogle Scholar
  25. Hansen, A. J., 1977, Extracellular potassium concentration in juvenile and adult rat brain cortex during anoxia, Acta Physiol. Scand., 99: 412–420.CrossRefGoogle Scholar
  26. Hansen, A. J., 1978, The extracellular potassium concentration in brain cortex following ischemia in hypo-and hyperglycemic rats, Acta Physiol. Scand., 102: 324–329.CrossRefGoogle Scholar
  27. Hansen, A. J., 1985, Effect of anoxia on ion distribution in the brain, Physiol. Rev., 65: 101–148.Google Scholar
  28. Heinemann, U., and Lux, H. D., 1975, Undershoots following stimulus-induced rises of extracellular potassium concentration in cerebral cortex of cat, Brain Res., 93: 63–76.CrossRefGoogle Scholar
  29. Hernández-Cacéres, J., Macias-Gonzales, R., Brozek, G., and Bure, J., 1987, Systemic ketamine blocks cortical spreading depression but does not delay the onset of terminal anoxic depolarization in rats, Brain Res., in press.Google Scholar
  30. Honey, C. R., Miljkovic, Z., and Mac Donald, J. F., 1985, Ketamine and phencyclidine cause a voltage dependent block of responses to L-aspartic acid, Neurosci. Lett., 61: 135–139.CrossRefGoogle Scholar
  31. Hossmann, K. A., 1971, Cortical steady potential, impedance and excitability changes during and after total ischemia of cat brain, Exp. Neurol., 32: 163–175.CrossRefGoogle Scholar
  32. Hossmann, K.-A., and Takagi, S., 1976, Osmolality of brain in cerebral ischemia, Exp. Neurol., 51: 124–131.CrossRefGoogle Scholar
  33. Huang, S. F.-L., and Sun, G. Y., 1987, Acidic phospholipids, diacylglycerols, and free fatty acids in gerbil brain: A comparison of ischemic changes resulting from carotid ligation and decapitation, J. Neurosci. Res., 17: 162–167.CrossRefGoogle Scholar
  34. Ito, U., Go, K. G., Walker, J. T. Jr., Spatz, M., and Klatzo, I., 1976, Experimental cerebral ischemia in mongolian gerbils. I. Light microscopic observations, Acta Neuropathol., 32: 209–223.CrossRefGoogle Scholar
  35. Kemp, J. A., Foster, A. C., and Wong, E. H. F., 1987, Non-competitive antagonists of excitatory amino acid receptors, Trends in Neurosci., 10: 294–298.CrossRefGoogle Scholar
  36. Koroleva, V. I., and Bures, J., 1980, Blockade of cortical spreading depression in electrically and chemically stimulated areas of cerebral cortex in rats, Electroenceph. clin. Neurophysiol., 48: 1–15.CrossRefGoogle Scholar
  37. Koroleva, V. I., and Bures, J., 1982, Stimulation induced recurrent epileptiform discharges block cortical and subcortical spreading depression in rats, Physiol. bohemoslov., 31: 385–400.Google Scholar
  38. Ktivdnek, J., 1981, In vivo electrical stimulation alters sensitivity of the brain (Na++K+)ATPase toward inhibition by vanadate, J. Neurobiol., 12: 343–352.CrossRefGoogle Scholar
  39. Krivdnek, J., and Bures, J., 1960, Ion shifts during Leao’s spreading cortical depression, Physiol. bohemoslov., 9: 494–503.Google Scholar
  40. Leao, A. A. P., 1944, Spreading depression of activity in the cerebral cortex, J. Neurophysiol., 7: 359–390.Google Scholar
  41. Leao, A. A. P., 1947, Further observations on the spreading depression of activity in the cerebral cortex, J. Neurophysiol., 10: 409–419.Google Scholar
  42. Astrup, J., Blennow, G., and Nilsson, B., 1980, Effect of reduced cerebral blood flow upon EEG pattern, cerebral extra-cellular potassium, and energy metabolism in the rat cortex during bicuculline-induced seizures, Brain Res., 177: 115–126.CrossRefGoogle Scholar
  43. Leao, A. A. P., and Martins-Ferreira, H. M., 1953, Alteracao da impedancia elétrica no decurso da depressao alastrante da atividade do córtex cerebral, An. Acad. Brasil. Ci., 25: 259–266.Google Scholar
  44. Lehmenkühler, A., Speckmann, F. J., and Caspers, H., 1976, Cortical spreading depression in relation to potassium activity, oxygen tension, local flow and carbon dioxide tension, in: “Ion and Enzyme Electrodes in Biology and Medicine”Google Scholar
  45. M. Kessler et al., eds., Urban and Schwarzenberg, Munich, pp. 311–315.Google Scholar
  46. Mareš, P., Krfz, N., Brozek, G., and Bures, J., 1976, Anoxic changes of extracellular potassium concentration in the cerebral cortex of young rats, Exp. Neurol., 53: 12–20.CrossRefGoogle Scholar
  47. Bure, J., Burešová, O., and Zacharovš, D., 1957, Effect of changes in body temperature on spreading EEG depression, Physiol. bohemoslov., 6: 454–461.Google Scholar
  48. Mayer, M. L., and Westbrook, G. L., 1987, The physiology of excitatory amino acids in the vertebrate central nervous system, Progress in Neurobiol., 28: 197–276.CrossRefGoogle Scholar
  49. Nicholson, C., and Kraig, R. P., 1981, The behavior of extra-cellular ions during spreading depression, in: “The Application of Ion-Selective Microelectrodes”, T. Zeuthen, ed., Elsevier, Amsterdam, pp. 217–238.Google Scholar
  50. Olney, J. W., Price, M. T., Fuller, T. A., Labruyere, J., Samson, L., Carpenter, M., and Mahan, K., 1986, The antiexcitotoxic effects of certain anesthetics, analgesics and sedative-hypnotics, Neurosci. Lett., 68: 29–34.CrossRefGoogle Scholar
  51. Phillips, J. M., and Nicholson, C., 1979, Anion permeability in spreading depression investigated with ion sensitive microelectrodes, Brain Res., 173: 567–571.CrossRefGoogle Scholar
  52. Prince, D. A., Lux, H. D., and Neher, E., 1973, Measurement of extracellular potassium activity in cat cortex, Brain Res., 50: 489–495.CrossRefGoogle Scholar
  53. Pulsinelli, W. A., Waldman, S., Rawlinson, D., and Plum, F., 1982, Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat, Neurology 32: 1239–1246.CrossRefGoogle Scholar
  54. Reddy, M. M., and Bures, J., 1980, Cortical ( K) and the stimulation induced blockade of spreading depression in the rat cerebral cortex, Neurosci. Lett., 17: 243–247.CrossRefGoogle Scholar
  55. Rehncrona, S., Rosén, I., and Siesjö, B. K., 1981, Brain lactic acidosis and ischemic cell damage. 1. Biochemistry and neuro-physiology, J. Cereb. Blood Flow Metab., 1: 297–311.CrossRefGoogle Scholar
  56. Ridge, J. W., 1967, Resting and stimulated respiration in vitro in the central nervous system, Biochem. J., 105: 831–835.Google Scholar
  57. Rothman, S. M., and Olney, J. W., 1987, Excitotoxicity and the NMDA receptor, Trends in Neurosci., 10: 299–302.CrossRefGoogle Scholar
  58. Siemkowicz, E., and Hansen, A. J., 1978, Clinical restitution following cerebral ischemia in hypo-, normo-, and hyperglycemic rats, Acta Neurol. Scand., 58: 1–8.CrossRefGoogle Scholar
  59. Siemkowicz, E., and Hansen, A. J., 1981, Brain extracellular ion composition and EEG activity following 10 minutes ischemia in normo-and hyperglycemic rats, Stroke, 12: 236–240.CrossRefGoogle Scholar
  60. Somjen, G. G., 1979, Extracellular potassium in the mammalian nervous system, Annu. Rev. Physiol., 41: 159–177.CrossRefGoogle Scholar
  61. Suzuki, R., Yamaguchi, T., Inaba, Y., and Wagner, H. G., 1985, Microphysiology of selectively vulnerable neurons, in: “Molecular Mechanisms of Ischemic Brain Damage”, Progress in Brain Research, Vol. 63, K. Vogure, K.-A. Hossmann, B. K. Siesjö, F. A. Welsh, eds., Elsevier, Amsterdam, pp. 59–68.CrossRefGoogle Scholar
  62. Sykovš E., 1983, Extracellular K+ accumulation in the central nervous system, Prog. Bìophys. molec. Biol., 42: 135–189.Google Scholar
  63. Symon, L., 1986, Progression and irreversibility in brain ischaemia, in: “Mechanisms of Secondary Brain Damage”, A. Baethmann, K. G. Go, A. Unterberg, eds., Plenum, New York, pp. 221–257.Google Scholar
  64. Ueda, M., and Bures, J., 1977, Differential effects of cortical spreading depression on epileptic foci induced by various convulsants, Electroenceph. clin. Neurophysiol., 43: 666–674.CrossRefGoogle Scholar
  65. Valcana, T., 1972, Developmental changes in ionic composition of the brain in hypo and hyperthyroidism, in: “Drugs and the Developing Brain”, A. Vernadakis, N. Weiner, eds., Plenum Press, New York, pp. 289–304.Google Scholar
  66. Van Harreveld, A., 1959, Components in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle, J. Neurochem., 3: 300–315.CrossRefGoogle Scholar
  67. Van Harreveld, A., 1966 “Brain Tissue Electrolytes”, Butter-worths, Washington.Google Scholar
  68. Van Harreveld, A., and Stamm, J. S., 1953, Effect of pentobarbital and ether in the spreading cortical depression, Am. J. Physiol., 173: 164–170.Google Scholar
  69. Vyskocil, F., Kffš, N., and Bures, J., 1972, Potassium-selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats, Brain Res., 39: 255–259.CrossRefGoogle Scholar
  70. Wieloch, T., 1985, Neurochemical correlates to selective neuronal vulnerability, in: “Molecular Mechanisms of IschemicGoogle Scholar
  71. Brain Damage“, Progress in Brain Research, Vol. 63, K. Vogure, K.-A. Hossmann, B. K. Siesjö, F. A. Welsh, eds., Elsevier, Amsterdam, pp. 69–85.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Jan Bureš
    • 1
  • Olga Burešová
    • 1
  1. 1.Institute of PhysiologyCzechoslovak Academy of SciencesPrague 4 — KrčCzechoslovakia

Personalised recommendations