Biochemical Factors and Mechanisms of Secondary Brain Damage in Cerebral Ischemia and Trauma

  • A. Baethmann
  • O. Kempski
Chapter
Part of the Advances in Neurochemistry book series (ANCH, volume 7)

Abstract

A distinction between primary and secondary manifestations of brain damage from acute insults, such as trauma, or ischemia is not only of scientific interest but also of the highest clinical significance. After all, prevention of secondary brain damage in patients with severe head injury or cerebral ischemia is the ultimate purpose of treatment, including the measures of emergency care. It can be assumed that the secondary sequelae of head injury are as important for the outcome as the primary insult is. Therefore, it is obvious that development of more effective forms of treatment requires a better understanding of the mechanisms underlying secondary brain damage. Manifestations of secondary brain damage can be defined on a neuropathological or pathophysiological basis. They have a wide spectrum reaching from macroscopic phenomena, such as brain swelling, to subtle processes, such as cytotoxic cell damage from distinct molecular mechanisms. This chapter is a summary of recent concepts and findings.

Keywords

Arachidonic Acid Cerebral Ischemia Brain Edema Brain Damage Severe Head Injury 
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.
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References

  1. Ames, A., and Nesbett, F. B., 1983a, Pathophysiology of ischemic cell death. I. Time of onset of irreversible damage; importance of different components of the ischemic insult, Stroke 14: 219–226.PubMedCrossRefGoogle Scholar
  2. Ames, A., and Nesbett, F. B., 1983b, Pathophysiology of ischemic cell death. II. Changes in plasma membrane permeability and cell volume, Stroke 14:227–233.PubMedCrossRefGoogle Scholar
  3. Ames, A., and Nesbett, F. B., 1983c, Pathophysiology of ischemic cell death. HI. Role of extracellular factors, Stroke 14:233–240.PubMedCrossRefGoogle Scholar
  4. Astrup, J., Symon, L., Branston N. M., and Lassen, N. A., 1977, Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia, Stroke 8:51–57.PubMedCrossRefGoogle Scholar
  5. Baethmann, A., 1978, Pathophysiological and pathochemical aspects of cerebral edema, Neurosurg. Rev. 1:85–100.CrossRefGoogle Scholar
  6. Baethmann, A., 1987a, Organversagen nach Trauma—der zerebrale Sekundärschaden, Melsunger Med. Mittlg. 59:53–61.Google Scholar
  7. Baethmann, A., 1987b, Mechanisms of secondary brain damage, in “Traumatic Brain Edema” (F Cohadon, A. Baethmann, K. G. Go, and J. D. Miller, eds.), Fidia Research Series, vol. 8, pp. 81–97, Liviana Press, Padua, Italy.Google Scholar
  8. Baethmann, A., Maier-Hauff, K., Schürer, L., Lange, M., Guggenbichler, C., Vogt, W., Jacob, K., and Kempski, O., 1989, Release of glutamate and of free fatty acids in vasogenic brain edema, J. Neurosurg. 70:578–591.PubMedCrossRefGoogle Scholar
  9. Barbour, B., Brew, H., and Attwell, D., 1988, Electrogenic glutamate uptake in glial cells is activated by intracellular potassium, Nature 335:433–435.PubMedCrossRefGoogle Scholar
  10. Baudry, M., and Lynch, G., 1980, Hypothesis regarding the cellular mechanisms responsible for long-term synaptic potentiation in the hippocampus, Exp. Neurol. 68:202–204.PubMedCrossRefGoogle Scholar
  11. Bazan N. G., and Rakowski, H., 1970, Increased levels of brain free fatty acids after electroconvulsive shock, Life Sci. 9:501–507.PubMedCrossRefGoogle Scholar
  12. Bazan N. G., and Rodriguez de Türco, E. B., 1980, Membrane lipids in the pathogenesis of brain edema. Phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia, Adv. Neurol. 28:197–205.PubMedGoogle Scholar
  13. Benjamin A. M., and Quastel, J. H., 1976, Cerebral uptakes and exchange diffusion in vitro of L-and D-glutamates, J. Neurochem 26:431–441.PubMedCrossRefGoogle Scholar
  14. Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N. H., 1984, Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis, J. Neurochem. 43:1369–1374.PubMedCrossRefGoogle Scholar
  15. Branston N. M., Strong A. J., and Symon, L., 1977, Extracellular potassium activity, evoked potential and tissue blood flow, J. Neurol. Sci. 32:305–321.PubMedCrossRefGoogle Scholar
  16. Chan, P.H., and Fishman, R. A., 1978, Brain edema: Induction in cortical slices by polyunsaturated fatty acids, Science 201:358–360.PubMedCrossRefGoogle Scholar
  17. Chan P. H., Longar, S., and Fishman, R. A., 1983, Phospholipid degradation and edema development in cold-injured rat brain, Brain Res. 227:329–337.CrossRefGoogle Scholar
  18. Chapman A. G., Engelsen, B., and Meldrum, B. S., 1987, 2-Amino-7-phosphonoheptanoic acid inhibits insulin-induced convulsions and striatal aspartate accumulation in rats with frontal cortical ablation, J. Neurochem. 49:121–127.PubMedCrossRefGoogle Scholar
  19. Choi, D. W., 1985, Glutamate neurotoxicity in cortical cell cultures is calcium dependent, Neurosci. Lett. 58:293–297.PubMedCrossRefGoogle Scholar
  20. Choi, D. W., 1987, Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity, Brain Res. 403:333–336.PubMedCrossRefGoogle Scholar
  21. Clark, W. G., 1979, Kinins and the peripheral and central nervous systems, in “Bradykinin, Kallidin, and Kallikrein” (E. G. Erdös, ed.), Handbook of Experimental Pharmacology, vol. 25, pp. 311–356, Springer-Verlag, Berlin.Google Scholar
  22. Deshpande, J., and Wieloch, T., 1985, Amelioration of ischemic brain damage by postischemic treatment with flunarizine, Neurol. Res. 7:27–29.PubMedGoogle Scholar
  23. Drejer, J., Larsson O. M., and Schousboe, A., 1982, Characterization of L-glutamate uptake into and release from astrocytes and neurons cultured from different brain regions, Exp. Brain Res. 47: 259–269.PubMedCrossRefGoogle Scholar
  24. Duverger, D., Benavides, J., Cudennec, A., MacKenzie, E. T., Scatton, B., Seylaz, J., and Verecchia, C., 1987, A glutamate antagonist reduces infarction size following focal cerebral ischaemia independently of vascular and metabolic changes, J. Cereb. Blood Flow Metab. 7(Suppl. 1):S144.CrossRefGoogle Scholar
  25. Erdös, E. G. (ed.), 1979, “Bradykinin, Kallidin and Kallikrein,” Handbook of Experimental Pharmacology, vol. 25, Supplement, Springer-Verlag, Berlin.Google Scholar
  26. Fonnum, F., 1984, Glutamate: A neurotransmitter in mammalian brain, J. Neurochem. 42:1–11.PubMedCrossRefGoogle Scholar
  27. Frey E. K., Kraut, H., Werle, E., Vogel, R., Zickgraf-Rüdel, G., and Trautschold, I. (eds), 1968, “Das Kallikrein-Kinin-System und seine Inhibitoren,” F Enke Verlag, Stuttgart, Germany.Google Scholar
  28. Gardiner, M., Nilsson, B., Rehncrona, S., and Siesjö, B. K., 1981, Free fatty acids in the rat brain in moderate and severe hypoxia, J. Neurochem. 36:1500–1505.PubMedCrossRefGoogle Scholar
  29. Garthwaite, G., and Garthwaite, J., 1987, Receptor-linked ionic channels mediate N-methyl-D-aspartate neurotoxicity in rat cerebellar slices, Neurosci. Lett. 83:241–246.PubMedCrossRefGoogle Scholar
  30. Gazendam M. D., Go, K. G., Van Zonten, A. K., 1979, Composition of isolated edema fluid in cold-induced brain edema, J. Neurosurg. 51:70–77.PubMedCrossRefGoogle Scholar
  31. Gill, R., Foster, C, Iversen, L., and Woodruff, G. N., 1987, Ischaemia-induced degeneration of hippocampal neurones in gerbils is prevented by systemic administration of MK-801, J. Cereb. Blood Flow Metab. 7(Suppl. 1):S153.Google Scholar
  32. Graham D. I., Adams J. H., and Doyle, D., 1978, Ischemic brain damage in fatal non-missile head injuries, J. Neurol. Sci. 39:213–234.PubMedCrossRefGoogle Scholar
  33. Henn, E A., Goldstein M. N., and Hamberger, A., 1974, Uptake of the neurotransmitter candidate glutamate by glia, Nature 249:663–664.PubMedCrossRefGoogle Scholar
  34. Hertz, L., 1979, Functional interactions between neurons and astrocytes. I. Turnover and metabolism of putative amino acid transmitters, Prog. Neurobiol. 13:277–323.PubMedCrossRefGoogle Scholar
  35. Ikeda, M., Yoshida, S., Busto, R., Santiso, M., and Ginsberg, M. D., 1986, Polyphosphoinositides as a probable source of brain free fatty acids accumulated at the onset of ischemia, J. Neurochem. 47: 123–132.PubMedCrossRefGoogle Scholar
  36. Kauer J. A., Malenka, R. C., and Nicoll, R. A., 1988, NMDA application potentiates synaptic transmission in the hippocampus, Nature 334:250–252.PubMedCrossRefGoogle Scholar
  37. Kauppinen R. A., Enkvist, K., Holopainen, I., and Akerman, K. E. O., 1988, Glucose deprivation depolarizes plasma membrane of cultured astrocytes and collapses transmembrane potassium and glutamate gradients, Neuroscience 26:283–289.PubMedCrossRefGoogle Scholar
  38. Kempski, O., 1982, “Die Lokalisation des Glutamat-induzierten Hirnödems,” Dissertation, Ludwig-Maximilians-University, Munich, Germany.Google Scholar
  39. Kempski, O., 1986, Cell swelling mechanisms in brain, NATO ASI Ser. A: Life Sci. 115:203–220.Google Scholar
  40. Kempski, O., Gross, U., and Baethmann, A., 1982, An in-vitro model of cytotoxic brain edema: Cell volume and metabolism of cultivated glial and nerve cells, Adv. Neurosurg. 10:254–258.CrossRefGoogle Scholar
  41. Kempski, O., Baethmann, A., Neu, A., Staub, F., 1986, Analysis of molecular mechanisms causing ischemic cell swelling in-vitro, in “Pharmacology of Cerebral Ischemia” (J. Krieglstein, ed.), pp. 131–139, Elsevier, Amsterdam.Google Scholar
  42. Kempski, O., Zimmer, M., Neu, A., von Rosen, F., Jansen, M., and Baethmann, A., 1987, Control of glial cell volume in anoxia. In vitro studies on ischemic cell swelling, Stroke 18:623–628.PubMedCrossRefGoogle Scholar
  43. Kempski, O., Staub, F., Jansen, M., Schödel, F., and Baethmann, A., 1988a, Glial swelling during extracellular acidosis in-vitro, Stroke 19:385–392.PubMedCrossRefGoogle Scholar
  44. Kempski, O., Staub, F., von Rosen, F., Zimmer, Neu, A., and Baethmann, A., 1988b, Molecular mechanisms of glial swelling in-vitro, Neurochem. Pathol. 9:109–126.PubMedGoogle Scholar
  45. Kim J. S., Claus, D., and Kornhuber, H. H., 1983, Cerebral glutamate, neuroleptic drugs and schizophrenia: Increase of cerebrospinal fluid glutamate levels and decrease of striate body glutamate levels following sulpiride treatment in rats, Eur. Neurol. 22:367–370.PubMedCrossRefGoogle Scholar
  46. Kontos H. A., Wei, E. P., Povlishock J. T., Dietrich W. D., Magiera C. J., and Ellis, E. F., 1980, Cerebral arteriolar damage by arachidonic acid and prostaglandin G2, Science 209:1242–1245.PubMedCrossRefGoogle Scholar
  47. Kraig R. P., Petito C. K., Plum, F., and Pulsinelli, W. A., 1987, Hydrogen ions kill brain at concentrations reached in ischemia, J. Cereb. Blood Flow Metab. 7:379–386.PubMedCrossRefGoogle Scholar
  48. Lowe, D. A., 1978, Morphological changes in the cat cerebral cortex produced by superfusion of ouabain, Brain Res. 148:347–363.PubMedCrossRefGoogle Scholar
  49. Lucas D. R., and Newhouse, J. P., 1957, The toxic effect of sodium l-glutamate on the inner layers of the retina, AMA Arch. Ophthalmol. 58:193–201.PubMedCrossRefGoogle Scholar
  50. Macknight, A. D. C., 1984, Cellular response to injury, in “Edema” (N. Staub and Taylor, eds.), pp. 489–520, Raven Press, New York.Google Scholar
  51. Macknight, A. D. C., and Leaf, A., 1977, Regulation of cellular volume, Physiol. Rev. 37:510–573.Google Scholar
  52. Maier-Hauff, K., Baethmann, A., Lange, M., Schürer, L., and Unterberg, A., 1984a, The kallikrein-kinin system as mediator in vasogenic brain edema. 2. Studies on kinin formation in focal and perifocal brain tissue, J. Neurosurg. 61:97–106.PubMedCrossRefGoogle Scholar
  53. Maier-Hauff, K., Baethmann, A., Vogt, W., Jacob, K., and Marguth, F., 1984b, Mediator compounds in CSF of neurosurgical patients with raised intracranial pressure, Adv. Neurosurg. 12:302–306.CrossRefGoogle Scholar
  54. Mayer M. L., and Westbrook, G. L., 1987a, Cellular mechanisms underlying excitotoxicity, Trends Neurosci. 10:59–61.CrossRefGoogle Scholar
  55. Mayer M. L., and Westbrook, G. L., 1987b, The physiology of excitatory amino acids in the vertebrate central nervous system, Prog. Neurobiol. 28:197–276.PubMedCrossRefGoogle Scholar
  56. Meldrum B. S., Evans, M. C., Swan J. H., and Simon, R. P., 1987, Protection against hypoxic-ischemic brain damage with excitatory amino acid antagonists, Med. Biol. 65:153–157.PubMedGoogle Scholar
  57. Nicoletti, F., Wroblewski J. T., Novelli, A., Alho, H., Guidotti, A., and Costa, E., 1986, The activation of inositol phospholipid metabolism as a signal-transducing system for excitatory amino acids in primary cultures of cerebellar granule cells, J. Neurosci. 6:1905–1911.PubMedGoogle Scholar
  58. Olney, J. W., and Sharpe, L. G., 1969, Brain lesions in an infant rhesus monkey treated with monosodium glutamate, Science 166:386–388.PubMedCrossRefGoogle Scholar
  59. Olney, J. W., Price, M. T., Fuller T. A., Labruyere, J., Samson, K., Carpenter, M., and Mahan, K., 1986, The anti-excitotoxic effects of certain anesthetics, analgetics and sedative-hypnotics, Neurosci. Lett. 68:29–34.PubMedCrossRefGoogle Scholar
  60. Onodera, H., Sato, G., and Kogure, K., 1986, Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells, Neurosci. Lett. 68:169–174.PubMedCrossRefGoogle Scholar
  61. Park C. K., Nehls D. G., Graham D. I., Teasdale G. M., and McCulloch, J., 1988, Focal cerebral ischaemia in the cat: Treatment with the glutamate antagonist MK-801 after induction of ischaemia, J. Cereb. Blood Flow Metab. 8:757–762.PubMedCrossRefGoogle Scholar
  62. Perry T. L., Hansen, S., and Kennedy, J., 1975, CSF amino acids and plasma-CSF amino acid ratios in adults, J. Neurochem. 24:587–589.PubMedCrossRefGoogle Scholar
  63. Politi L. E., Rodriguez de Turco E. B., and Bazan, N. G., 1985, Dexamethasone effect on free fatty acid and diacylglycerol accumulation during experimental induced vasogenic brain edema, Neurochem. Pathol. 3:249–269.PubMedGoogle Scholar
  64. Reynolds I. J., and Miller, R. J., 1988, Multiple sites for the regulation of the N-methyl-D-aspartate receptor, Mol. Pharmacol. 33:581–584.PubMedGoogle Scholar
  65. Rothenfusser, W., 1982, Die Bedeutung von Glutamat als Hirnödemfaktor, Dissertation, Ludwig-Maximilians-University, Munich, Germany.Google Scholar
  66. Rothman S. M., and Olney, J. W., 1986, Glutamate and the pathophysiology of hypoxic-ischemic brain damage, Ann. Neurol. 19:105–111.PubMedCrossRefGoogle Scholar
  67. Rothman S. M., and Olney, J. W., 1987, Excitotoxicity and the NMDA receptor, Trends Neurosci. 10: 299–302.CrossRefGoogle Scholar
  68. Sato, K., Yamaguchi, M., Mullan, S., Evans, J. P., and Ishii, S., 1969, Brain edema: A study of biochemical and structural alterations, Arch. Neurol. 21:413–424.PubMedCrossRefGoogle Scholar
  69. Shank, R. P., and Aprison, M. H., 1981, Present status and significance of the glutamine cycle in neural tissues, Life Sci. 28:837–842.PubMedCrossRefGoogle Scholar
  70. Shaw, C.M., Alvord, E. C., and Berry, R. G., 1959, Swelling of the brain following ischemic infarction with arterial occlusion, Arch. Neurol. 1:161–177.PubMedCrossRefGoogle Scholar
  71. Siesjö, B. K., 1988, Mechanisms of ischemic brain damage, Crit. Care Med. 16:954–963.PubMedCrossRefGoogle Scholar
  72. Siesjö, B. K., and Wieloch, T., 1986, Epileptic brain damage: Pathophysiology and neurochemical pathology, Adv. Neurol. 44:813–847.PubMedGoogle Scholar
  73. Simon, R. P, Swan J. H., Griffiths, T., and Meldrum, B. S., 1984, Blockade of N-methyl-D-aspartate receptors may protect against ischaemic damage in the brain, Science 226:850–852.PubMedCrossRefGoogle Scholar
  74. Staub, F., Baethmann, A., Peters, J., and Kempski, O., 1990, Effects of lactacidosis on volume and viability of glial cells, Acta Neurochirg. (Suppl. 51), 3–6.Google Scholar
  75. Staub, F., Baethmann, A., Peters, G., Weigt, H., and Kempski, O., 1990, Effects of lactacidosis on glial cell volume and viability, J. Cereb. Blood Flow Metab. 10:866–876.PubMedCrossRefGoogle Scholar
  76. Symon, L., 1986, Progression and irreversibility in brain ischaemia, NATO ASI Ser. A: Life Sci. 115: 221–237.Google Scholar
  77. Unterberg, A., and Baethmann, A., 1984, The kallikrein-kinin system as mediator in vasogenic brain edema. 1. Cerebral exposure to bradykinin and plasma, J. Neurosurg. 61:87–96.PubMedCrossRefGoogle Scholar
  78. Unterberg, A., Wahl, M., and Baethmann, A., 1984, Effects of bradykinin on permeability and diameter of pial vessels in vivo, J. Cereb. Blood Flow Metab. 4:574–585.PubMedCrossRefGoogle Scholar
  79. Unterberg, A., Dautermann, C., Baethmann, A., and Müller-Esterl, W., 1986, The kallikrein-kinin system as mediator in vasogenic brain edema. 3. Inhibition of the kallikrein-kinin system in traumatic brain swelling, J. Neurosurg. 64:269–276.PubMedCrossRefGoogle Scholar
  80. Unterberg, A., Wahl, M., Hammersen, F., and Baethmann, A., 1987, Permeability and vasomotor response of cerebral vessels during exposure to arachidonic acid, Acta Neuropathol. 73:209–219.PubMedCrossRefGoogle Scholar
  81. Unterberg, A., Wahl, M., and Baethmann, A., 1988, Effects of free radicals on permeability and vasomotor response of cerebral vessels, Acta Neuropathol. 76:238–244.PubMedCrossRefGoogle Scholar
  82. Van Harreveld, A., 1959, Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle, J. Neurochem. 3:300–315.CrossRefGoogle Scholar
  83. Van Harreveld, A., 1972, The extracellular space in the vertebrate central nervous system, in “The Structure and Function of Nervous Tissue IV” (G. H. Bourne, ed.), pp. 447–511, Academic Press, New York.CrossRefGoogle Scholar
  84. Van Harreveld, A., and Fifkova, E., 1973, Mechanisms involved in spreading depression, J. Neurobiol. 4:375–387.PubMedCrossRefGoogle Scholar
  85. Van Harreveld, A., and Fifkova, E., 1975, A mechanism for potentiation and short term memory, Proc. K. Ned. Akad. Wet. Ser. C. 78:21–24.Google Scholar
  86. Wahl, M., Unterberg, A., Baethmann, A., and Schilling, L., 1988, Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema, J. Cereb. Blood Flow Metab. 8:621–634.PubMedCrossRefGoogle Scholar
  87. Watkins, J. C., 1981, Pharmacology of excitatory amino acid receptors, in “Glutamate: Transmitter in the Central Nervous System” (G. Roberts, A. Storm-Mathisen, and R. Johnston, eds.), pp. 1–24, John Wiley & Sons, New York.Google Scholar
  88. Weiss, S., Schmidt B. H., Sebben, M., Kemp D. E., Bockaert, J., and Sladeczek, F., 1988, Neurotransmitter-induced inositol phosphate formation in neurons in primary culture, J. Neuro-chem. 50:1425–1433.Google Scholar
  89. Wieloch, T., Lindvall, O., Blomqvist, P., and Gage, E H., 1985, Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant pathway, Neurol. Res. 7:24–26.PubMedGoogle Scholar
  90. Yu, A. C. H., Gregory G. A., and Chan, P.H., 1989, Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures, J. Cereb. Blood Flow Metab. 9:20–28.PubMedCrossRefGoogle Scholar
  91. Zanotto, L., and Heinemann, U., 1983, Aspartate and glutamate induced reductions in extracellular free calcium and sodium concentration in area CA1 of ”in vitro“hippocampal slices of rats, Neurosci. Lett. 35:79–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • A. Baethmann
    • 1
    • 2
  • O. Kempski
    • 1
    • 2
  1. 1.Institute for Surgical Research, Klinikum GrosshadernLudwig Maximilians UniversityMünchen 70Germany
  2. 2.Institute of Neurosurgical PathophysiologyUniversity of MainzMainzGermany

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