Cellular Mechanisms Involved in Generation of Brain Edema

  • U. Heinemann
  • J. Sarvey


Brain edema is a general complication of many central nervous system disorders of infectious, vascular, tumor, hypoxic or epileptic origin. Two major causes determine the pathophysiology of brain edema. These can be distinguished by changes in the size of the extracellular space (ES). The first results from breakdown of the blood-brain barrier with transfer of proteins from blood vessels into the ES [5] with a consequent increase in the size of the ES, in brain volume and in intracranial pressure. Interestingly, such edema is often more marked in white than in grey matter, which may point to active volume regulatory properties in astrocyte and nerve cell rich grey matter.


Glial Cell NMDA Receptor Brain Edema Excitatory Amino Acid NMDA Receptor Antagonist 
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  1. 1.
    B. Ault, R. H. Evans, A. A. Francis, D. J. Oakes and J. C. Watkins, Selective depression of excitatory amino acid induced depolarization by magnesium ions in isolated spinal cord, J. Physiol. London, 307: 413–428 (1980).PubMedCentralPubMedGoogle Scholar
  2. 2.
    G. F. Ayala, M. Dichter, R. J. Gumnit, M. Matsumoto and W. A. Spencer, Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggest a neurophysiological explanation of brief paroxsyms, Brain Res., 52: 1–17 (1973).Google Scholar
  3. 3.
    C. Benninger, J. Kadis and D. A. Prince, Extracellular calcium and potassium changes in hippocampal slices, Brain Res., 187: 165–182 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    R. S. Bourke and K. M. Nelson, Further studies on the K+-dependent swelling of primate cerebral cortex in vivo, J. Neurochem., 19: 663–685 (1972).PubMedCrossRefGoogle Scholar
  5. 5.
    J. Cervos-Navarro and R. Ferszt, eds, “Advances in Neurology 28, Brain Edema”, Raven Press, New York (1980).Google Scholar
  6. 6.
    E. J. Coan and G. L. Collingridge, Magnesium ions block an N-methyl-Daspartate receptor mediated component of synaptic transmission in rat hippocampus, Neurosci. Lett., 53: 21–26 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    R. C. Collins, C. Kennedy, L. Sokoloff and F. Plum, Focal cortical seizures induce distant thalamic lesions, Arch. Neurol., 33: 356–542 (1976).CrossRefGoogle Scholar
  8. 8.
    M. Croucher, J. F. Collins and B. S. Meldrum, Anticonvulsant action of excitatory amino acid antagonists, Science, 216: 899–901 (1982).PubMedCrossRefGoogle Scholar
  9. 9.
    I. Dietzel, U. Heinemann, G. Hofmeier and H. D. Lux, Transient changes in the size of extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration, Exp. Brain Res., 40: 432–439 (1980).PubMedGoogle Scholar
  10. 10.
    I. Dietzel, U. Heinemann, G. Hofmeier and H. D. Lux, Stimulus induced changes in extracellular Na+ and Cl-concentration in relation to changes in the size of the extracellular space, Exp. Brain Res., 46: 7384 (1982).Google Scholar
  11. 11.
    I. Dietzel and U. Heinemann, Extracellular electrolyte changes during enhanced neuronal activity can be explained by spatial glial K+ buffering in addition to small decreases in osmotic-pressure possibly induced by increases in metabolic activity, in: “Cerebral Blood Flow, Metabolism and Epilepsy”, M. Baldy-Moulinier, D. H. Ingvar and B. S. Meldrum, eds., John Libbey, London, pp 195–201 (1983).Google Scholar
  12. 12.
    I. Dietzel and U. Heinemann, Dynamic variations of the brain cell micro-environment in relation to neuronal hyperactivity, Ann. NY Acad. Sci., 481: 72–86 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    R. Dingledine, Involvements of N-methyl-D-aspartate receptors in epileptiform bursting in rat hippocampal slice, Trends Neurosci., 9: 47–49 (1986).CrossRefGoogle Scholar
  14. 14.
    J. L. Farber, The role of calcium in cell death, Life Science, 29: 1289–1295 (1981).CrossRefGoogle Scholar
  15. 15.
    K. J. Futamachi and T. A. Pedley, Glial cells and extracellular potassium. Their relationship in mammalian-cortex, Brain Res., 109: 311–322 (1976).PubMedCrossRefGoogle Scholar
  16. 16.
    A. R. Gardner-Medwin, Possible roles of vertebrate neuroglia in potassium dynamics, spreading depression and migraine, Exp. Biol., 95: 111–127 (1981).Google Scholar
  17. 17.
    A. R. Gardner-Medwin, Analysis of potassium dynamics in mammalian brain tissue, J. Physiol. London, 335: 393–426 (1983).PubMedCentralPubMedGoogle Scholar
  18. 18.
    A. R. Gardner-Medwin, A study of the mechanisms by which potassium moves through brain tissue in the rat, J. Physiol., 335: 353–374 (1983).PubMedCentralPubMedGoogle Scholar
  19. 19.
    T. M. Grisar, Neuron glial relationship in human and experimental epilepsy: a biochemical point of view, Adv. Neurol., 44: 1045–1073 (1986).Google Scholar
  20. 20.
    M. J. Gutnick, B. W. Connors and B. R. Ransom, Dye-coupling between glial cells in the guinea pig neocortical slice, Brain Res., 213: 486–492 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    B. Hamon and U. Heinemann, Effects of GABA and bicuculine on Nmethyl-D-aspartate and quiqualate induced reduction in extracellular free calcium in area CAl of the hippocampal slice, Exp. Brain Res., 64: 27–36 (1986).PubMedGoogle Scholar
  22. 22.
    A. J. Hansen, Effect of anoxia on ion distribution in the brain, Physiol. Rev., 65: 101–148 (1985).PubMedGoogle Scholar
  23. 23.
    R. J. Harris and L. Symon, Extracellular pH, potassium and calcium activities in progressive ischemia of rat cortex, J. Cereb. Blood Flow Metab., 4: 178–186 (1984).PubMedCrossRefGoogle Scholar
  24. 24.
    U. Heinemann, Basic mechanisms of the epilepsies, in: “Textbook of Clinical Neurophysiology”, A. M. Halliday, S. R. Butler and R. Paul, eds., John Wiley, pp 497–534 (1987).Google Scholar
  25. 25.
    U. Heinemann, in: “Cerebral Blood Flow”e Epileptic Focus”, Wieser et al., eds., John Libbey, London, Paris, pp 27–44 (1987).Google Scholar
  26. 26.
    U. Heinemann and I. Dietzel, Extracellular potassium concentration in chronic aluminia cream foci of cats, J. Neurophysiol., 52: 421–434 (1984).PubMedGoogle Scholar
  27. 27.
    U. Heinemann and M. J. Gutnick, Relation between extracellular potassium concentration and neuronal activities in cat thalamus (VPL) during projection of cortical epileptiform discharges, Electroenceph. Clin. NeurophysioL, 47: 345–357 (1979).PubMedCrossRefGoogle Scholar
  28. 28.
    U. Heinemann and B. Hamon, Calcium and epileptogenesis, Exp. Brain Res., 65: 1–10 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    U. Heinemann, A. Konnerth, R. Pumain and W. Wadman, Extracellular calcium and potassium concentration changes in chronic epileptic tissue, Adv. Neurol., 44: 641–661 (1986).PubMedGoogle Scholar
  30. 30.
    U. Heinemann, H. D. Lux, M. G. Marciani and G. Hofmeier, Slow potentials in relation to changes in extracellular potassium activity in the cortex of cats, in: “Origin of Cerebral Field Potentials”, E. J. Speckmann and H. Caspers, eds., Georg Thieme, Stuttgart, pp 33–48 (1979).Google Scholar
  31. 31.
    U. Heinemann, H. D. Lux and M. J. Gutnick, Extracellular free calcium and potassium during paroxysmal discharges in the cerebral cortex of the cat, Exp. Brain Res., 7: 237–243 (1977).Google Scholar
  32. 32.
    U. Heinemann, S. Neuhaus and I. Dietzel, I. Aspects of K+ regulation in normal and gliotic brain tissue, in: “Cerebral Blood Flow, Metablism and Epilepsy”, M. Baldy-Moulinier, D. H. Ingvar and B. S. Meldrum, eds., John Libbey, London, pp 271–278 (1983).Google Scholar
  33. 33.
    U. Heinemann and R. Pumain, Extracellular calcium activity in cat sensorimotor cortex induced by iontophoretic application of amino acids, Exp. Brain Res., 40: 247–250 (1980).PubMedGoogle Scholar
  34. 34.
    N. Hod, J. M. H. French-Mullen and D. O. Carpenter, Kainic acid responses and toxicity show pronounced Ca dependence, Brain Res., 358: 380–384 (1985).CrossRefGoogle Scholar
  35. 35.
    K. A. Hossmann, Cortical steady potentials, impedance and excitability changes during and after total ischemia of the cat brain, Exp. Neurol., 32: 163–175 (1971).PubMedCrossRefGoogle Scholar
  36. 36.
    K. A. Hossmann, S. Sakaki and V. Zimmermann, Cation activities in reversible ischemia of the cat brain, Stroke, 8: 77–81 (1977).PubMedCrossRefGoogle Scholar
  37. 37.
    J. Janus, E. J. Speckmann and A. Lehmenkühler, Relations between extracellular K+ and Ca2+ activities and local field potentials in the spinal cord of the rat during focal and generalized seizure discharges, in: “Ion-Selective Microelectrodes and their Use in Excitable Tissues”, E. Sykova, P. Hnik and L. Viklicky, eds., Plenum Press, New York and London, pp 181–185 (1981).CrossRefGoogle Scholar
  38. 38.
    H. Kettenmann and M. Schachner, Pharmacological properties of gamma aminobuytric acid, glutamate and aspartate induced depolarizations in cultured astrocytes, J. Neurosci., 5: 3295–3301 (1985).PubMedGoogle Scholar
  39. 39.
    H. Kettenmann, U. Sonnhof and M. Schachner, Exclusive potassium dependence of the membrane potential in cultured mouse oligodendrocytes, J. Neurosci., 3: 500–505 (1983).PubMedGoogle Scholar
  40. 40.
    G. Köhr and U. Heinemann, Anticonvulsive properties of ketamin and 2aminophosphonovalerate in the low magnesium epilepsy in rat hippocampal slices, Neurosci. Res. Commun., 1: 17–21 (1987).Google Scholar
  41. 41.
    A. Konnerth, Y. Yaari and U. Heinemann, Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro, J.Neurophysiol., 56: 409–423 (1986).PubMedGoogle Scholar
  42. 42.
    R. P. Kraig and C. Nicholson, Extracellular ionic variations during spreading depressions, Neurosci., 3: 1045–1059 (1978).CrossRefGoogle Scholar
  43. 43.
    J. D. C. Lambert and U. Heinemann, Extracellular calcium changes accompanying the action of excitatory amino acids in area CA1 of the hippocampus. Possible implications for the initiation and spread of epileptic discharges, in: “Epilepsy and Calcium”, E. J. Speckmann et al., eds., Urban und Schwarzenberg, München, pp 35–62 (1986).Google Scholar
  44. 44.
    A. A. P. Leao, Spreading depression of activity in the cerebral cortex, J. Neurophysiol., 7: 359–390 (1944).Google Scholar
  45. 45.
    A. Lehmenkühler, W. Zidek and H. Caspers, Changes of extracellular Na+ and Cl--activities in the brain cortex during seizure discharges, in: “Physiology and Pharmacology of Epileptogenic Phenomena”, M. R. Klee, H. D. Lux and E. J. Speckmann, eds., Raven Press, New York, pp 37–45 (1982).Google Scholar
  46. 46.
    H. D. Lux, U. Heinemann and I. Dietzel, Ionic changes and alterations in the size of the extracellular space during epileptic activity, Adv. Neurol., 44: 619–639 (1986).PubMedGoogle Scholar
  47. 47.
    M. L. Mayer, G. L. Westbrook and P. B. Guthrie, Voltage-dependent block of Mgt of NMDA-responses in spinal cord neurones, Nature, 309: 250–263 (1984).CrossRefGoogle Scholar
  48. 48.
    A. B. MacDermott, M. L. Mayer, G. L. Westbrook, S. J. Smith and J. L. Barker, NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones, Nature, 321: 519–522 (1986).PubMedCrossRefGoogle Scholar
  49. 49.
    B. S. Meldrum, J. J. Croucher, S. J. Czucwar, J. F. Collins, K. Curry, M. Joseph and T. W. Stone, A comparison of the anticonvulsant potency of (+-)2-amino-phosphonovaleric acid and (+-)2-amino-7-phosphonoheptanoic acid, Neuroscience, 9: 925–930 (1983).PubMedCrossRefGoogle Scholar
  50. 50.
    I. Mody and U. Heinemann, Laminar profile of the changes in extracellular calcium concentration induced by repetitive stimulation and excitatory amino acids in the rate dentate gyrus, Neurosci. Lett., 69: 137–142 (1986).PubMedCrossRefGoogle Scholar
  51. 51.
    I. Mody, J. D. C. Lambert and U. Heinemann, Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices, J. Neurophysiol., 57: 869–888 (1987).PubMedGoogle Scholar
  52. 52.
    C. Nicholson, Dynamics of the brain cell microenvironment, NRP Bulletin, 18: 172–322 (1980).Google Scholar
  53. 53.
    C. Nicholson and J. M. Phillips, Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum, J. PhysioL London, 321: 225–258 (1981).PubMedCentralPubMedGoogle Scholar
  54. 54.
    L. Nowak, O. P. Bregestowski, P. Ascher, A. L. Herbet and A. Prochiantz, Magnesium gates glutamate-activated channels in mouse central neurones, Nature, 307: 462–464 (1984).PubMedCrossRefGoogle Scholar
  55. 55.
    J. W. Olney, R. C. Collins and R. S. Sloviter, Excitotoxic mechanisms of epileptic brain damage, Adv. NeuroL, 44: 857–878 (1986).Google Scholar
  56. 56.
    R. F. Orkand, Functional consequences of ionic changes resulting from electrical activity, Fed. Proc., 39: 1514–1543 (1980).Google Scholar
  57. 57.
    R. Pumain and U. Heinemann, Stimulus and amino-acid induced calcium and potassium changes in the rat neocortex, J. NeurophysioL, 53: 1–16 (1985).PubMedGoogle Scholar
  58. 58.
    J. B. Ranck, Specific impedance of cerebral cortex during spreading depression and an analysis of neuronal, neuroglial and interstitial contributions, Exp. Neurol., 9: 1–16 (1964).CrossRefGoogle Scholar
  59. 59.
    B. K. Siesjö, Cell damage in the brain: a speculative synthesis, J. Cerebral Blood Flow Metab., 1: 155–185 (1981).CrossRefGoogle Scholar
  60. 60.
    B. K. Siesjö and T. Wieloch, Epileptic brain damage: pathophysiology and neurochemical pathology, Adv. Neurol., 44: 813–848 (1986).PubMedGoogle Scholar
  61. 61.
    S. M. Rothman, The neurotoxicity of excitatory amino acid is produced by passive chloride influx, Neuroscience, 5: 1483–1489 (1985).PubMedGoogle Scholar
  62. 62.
    G. G. Somjen, Electrogenesis of sustained potentials, Prog. Neurobiol., 1: 201–232 (1973).PubMedGoogle Scholar
  63. 63.
    G. G. Somjen, Neuroglia and spinal fluids, J. Exp. Biol., 95: 129–133 (1981).PubMedGoogle Scholar
  64. 64.
    G. G. Somjen, Stimulus evoked and seizure related responses of extracellular calcium activity in spinal cord compared to those in cerebral cortex, J. NeurophysioL, 44: 617–632 (1980).PubMedGoogle Scholar
  65. 65.
    E. Sykova, Extracellular K+ accumulation in the central nervous system, Prog. Biophys. Mot. Biol., 42: 135–189 (1983).CrossRefGoogle Scholar
  66. 66.
    A. M. Thomson, D. C. West and D. Lodge, A N-methyl-D-aspartate receptor mediated synapse in rat cerebral cortex: a site of action of ketamine, Nature, 313: 479–481 (1985).PubMedCrossRefGoogle Scholar
  67. 67.
    A. Van Harreveld, J. Crowell and S. K. Malhotra, A study of extracellular space in central nervous tissue by freeze substitution, J. Cell. BioL, 25: 117–137 (1985).CrossRefGoogle Scholar
  68. 68.
    A. Van Harreveld, T. Murphy and K. W. Nobel, Specific impedance of rabbit cortical tissue, Am. J. Physiol, 205: 203–207 (1963).Google Scholar
  69. 69.
    S. S. Varon and G. G. Somjen, Neuron-glia interaction, Neurosci. Res. Prog. BulL, 17: 1–238 (1979).Google Scholar
  70. 70.
    H. Walther, J. D. C. Lambert, R. S. G. Jones, U. Heinemann and B. Hamon, Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium, Neurosci. Lett., 69: 156–161 (1986).PubMedCrossRefGoogle Scholar
  71. 71.
    W. Walz and L. Hertz, Ouabain-sensitive and ouabain-resistant net uptake of potassium into astrocytes and neurones in primary cultures. II. Role of extracellular potassium, J. Neurochem., 39: 70–77 (1982).PubMedCrossRefGoogle Scholar
  72. 72.
    J. C. Watkins and R. H. Evans, Excitatory amino acid transmitters, Ann. Rev. Pharmacol. Toxicol., 21: 165–204 (1981).CrossRefGoogle Scholar
  73. 73.
    Y. Yaari, A. Konnerth and U. Heinemann, Nonsynaptic epileptogenesis of the mammalian hippocampus in vitro, J. Neurophysiol., 56: 424–438 (1986).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • U. Heinemann
    • 1
  • J. Sarvey
    • 1
  1. 1.Institute for Normal and Pathological PhysiologyUniversity of KölnKöln 41Germany

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