Advertisement

Cerebral Metabolism in Hypoxia and Ischemia — Therapeutic Implications

  • B. K. Siesjö

Abstract

Cerebrovascular disease is one of the major causes of death. In the United States, for example, stroke exacts a greater toll than that of all other diseases except heart disease and cancer. Thus, close to 500 000 persons are affected by the disease each year, the estimated number of fatal cases being around 150 000 (Hachinski and Norris 1985). At present, the number of survivors are about 2 million. Figures are comparable in most other countries.

Keywords

Middle Cerebral Artery Occlusion Cerebral Perfusion Pressure Excitatory Amino Acid NMDA Antagonist Cereb Blood Flow 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aisen P (1979) Some physiochemical aspects of iron metabolism. In: CIBA Foundation Symposium, No. 51: Iron metabolism. Elsevier, Amsterdam, pp 1–17Google Scholar
  2. Alberti KGMM, Cuthbert C (1982) The hydrogen ion in normal metabolism: a review. In: Porter R, Lawrenson G (eds) Metabolic acidosis. CIBA Foundation Symposium 87. London, Pitman Books Ltd, pp 1–19Google Scholar
  3. Andiné P, Jacobson I, Hagberg H (1988) Calcium uptake evoked by electrical stimula tion is enhanced postischemically and precedes delayed neuronal death in CA1 of rat hippocampus: involvement of Af-methyl-D-aspartate receptors. J Cereb Blood Flow Metab 8:799–807PubMedGoogle Scholar
  4. Ascher P, Nowak L (1987) Electrophysiological studies of NMD A receptors. TINS 10(7):284–288Google Scholar
  5. Aust SD, Morehorse LA, Thomas CE (1985) Role of metals in oxygen radical reactions: hypothesis paper. J Free Radic Biol Med 1:3–25PubMedGoogle Scholar
  6. Babbs CF (1985) Role of iron ions in the genesis of reperfusion injury following successful cardiopulmonary resuscitation: preliminary data and a biochemical hypothesis. Ann Emerg Med 14:777–783PubMedGoogle Scholar
  7. Barber AA, Bernheim F (1967) Lipid peroxidation: its measurement, occurrence, and significance in animal tissues. Adv Gerontol Res 2:355–403PubMedGoogle Scholar
  8. Bazan (1976) Free arachidonic acid and other lipids in the nervous system during early ischemia and after electroshock. Adv Exp Med Biol 72:317–335PubMedGoogle Scholar
  9. Benveniste H, Jørgensen MB, Diemer NH, Hansen AJ (1988) Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. Acta Neurol Scand 78:529–536PubMedGoogle Scholar
  10. Berridge MJ (1984) Inositol triphosphate and diacylglycerol as second messengers. Biochem J 221:345–360Google Scholar
  11. Berridge MJ (1987) Inositol triphosphate and diacylglycerol: two interacting second messengers. Ann Rev Biochem 56:159–193PubMedGoogle Scholar
  12. Boris-Möller F, Drakenberg T, Elmdén K, Forsén S, Siesjö BK (1988) Evidence against major compartmentalization of H+ in ischemic rat brain tissue. Neurosci Lett 85:113–118PubMedGoogle Scholar
  13. Boris-Möller F, Smith M-L, Siesjö BK (1989) Effects of hypothermia on brain ischemia: a comparison of intraischemic and postischemic hypothermia. J Cereb Blood Flow Metab 9(Suppl):5276Google Scholar
  14. Branston NM, Strong AJ, Symon L (1977) Extracellular potassium activity, evoked po tential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex. J Neurol Sci 32:305–321PubMedGoogle Scholar
  15. Busto R, Dietrich WD, Globus MY-T, Valdés I, Scheinberg P, Ginsberg M (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7:729–738PubMedGoogle Scholar
  16. Carafoli E (1982) The regulation of intracelular calcium. Adv Exp Med Biol 151:461–472PubMedGoogle Scholar
  17. Carafoli E (1987) Intracellular calcium homeostasis. Annu Rev Biochem 56:395–433PubMedGoogle Scholar
  18. Carter C, Benavides J, Legendre P, Vincent JD, Noel F, Thuret F, Lloyd KG, Arbilla S, Zivkovic B, MacKenzie ET, Scatton B, Langer SZ (1988) Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. II. Evidence for 7V-methyl-D-aspartate receptor antagonist properties. J Pharmacology and Experimental Therapeutics 247(3):1222–1232Google Scholar
  19. Chan PH, Fishman RA (1985) Brain edema. In: Lajtha A (ed) Handbook of neurochemistry, vol 10. Plenum, New York, NY, pp 153–174Google Scholar
  20. Chan PH, Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology 34:315–320PubMedGoogle Scholar
  21. Chan PH, Longar S, Fishman RA (1987) Protective effects of liposome-entrapped Superoxide dismutase on posttraumatic brain edema. Ann Neurol 21:540–547PubMedGoogle Scholar
  22. Chien KR, Reeves JP, Buja LM, Bonte F, Parkey RW, Willerson JT (1981) Phospholipid alterations in canine ischemic myocardium. Temporal and topographical correlations with Tc-99m-PPi accumulation and in vitro sarcolemmal Ca2 + permeability defect. Circ Res 48:711–719PubMedGoogle Scholar
  23. Choi DW (1985) Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci Lett 58:293–297PubMedGoogle Scholar
  24. Choi DW (1987) Ionic dependence of glutamate neurotoxicity. J Neurosci 7:369–379PubMedGoogle Scholar
  25. Choi DW (1988 a) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634PubMedGoogle Scholar
  26. Choi DW (1988 b) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. TINS 11:465–469PubMedGoogle Scholar
  27. Choi DW, Koh J-Y, Peter S (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci 8(1):185–196PubMedGoogle Scholar
  28. Clark GD, Rothman SM (1987) Blockade of excitatory amino acid receptors protects anoxic hippocampal slices. Neurosci 21:665–761Google Scholar
  29. Crichton RR (1979) Interactions between iron metabolism and oxygen activation. In: Oxygen free radicals and tissue damage. Ciba Foundation Symposium 65. New York, Excerpta Medica, pp 57–72Google Scholar
  30. Demoupolos H, Flamm E, Seligman M, Power R, Pietronigro D, Ransohoff J (1977) Molecular pathology of lipids in CNS membranes. In: Jöbsis FF (ed) Oxygen and physiological function. Dallas, Texas, Professional Information Library, pp 491– 508Google Scholar
  31. Denton RM, McCormack JG (1985) Ca2 + transport by mammalian mitochondria and its role in hormone action. Am J Physiol 249:E543–E554PubMedGoogle Scholar
  32. Deshpande JK, Wieloch T (1986) Flunarizine, a calcium entry blocker, ameliorates ischemic brain damage in the rat. Anesthesiology 64:215–224PubMedGoogle Scholar
  33. Deshpande JK, Siesjö BK, Wieloch T (1987) Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. J Cereb Blood Flow Metab 7:89–95PubMedGoogle Scholar
  34. Fagg GE, Foster AC, Ganong AH (1986) Excitatory amino acid synaptic mechanisms and neurological function. TIPS -September: 357–363Google Scholar
  35. Färber JL (1981) The role of calcium in cell death. Life Sci 29:1289–1295PubMedGoogle Scholar
  36. Flamm ES, Demopoulos HB, Seligman ML et al. (1978) Free radicals in cerebral isch emia. Stroke 9:445–447PubMedGoogle Scholar
  37. Fleckenstein A, Janke J, Doring HJ, Leder O (1974) Myocardial fiber necrosis due to intracellular Ca overload -a new principle in cardiac hypertrophy. Rec Adv Stud Cardiac Struct Metab 4:563–568Google Scholar
  38. Folbergrová J, Ljunggren B, Norberg K, Siesjö BK (1974) Influence of complete ischemia on glycolytic metabolites, citric acid cycle intermediates, and associated amino acids in the rat cerebral cortex. Brain Res 80:265–279PubMedGoogle Scholar
  39. Foster AC, Fagg GE (1987) Taking apart NMDA receptors. Nature (London) 329:395–396Google Scholar
  40. Gardiner A, Smith M-L, Kågström E, Shohami E, Siesjö BK (1982) Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism. J Cereb Blood Flow Metab 2:429–438PubMedGoogle Scholar
  41. Garthwaite G, Hajos F, Garthwaite J (1986) Ionic requirements for neurotoxic effects of excitatory amino acid analogues in rat cerebellar slices. Neurosci 18:437–447Google Scholar
  42. Gebicki JM, Bielski BHJ (1981) Comparison of the capacities of the perhydroxyl and the Superoxide radicals to initiate chain oxidation of linoleic acid. J Am Chem Soc 103(23):7020–7022Google Scholar
  43. Gotoh O, Mohamed AA, McCulloch J, Graham DI, Harper AM, Teasdale GM (1986) Nimodipine and the haemodynamic and histopathological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 6:321–331PubMedGoogle Scholar
  44. Gotti B, Duverger D, Bertin J, Carter C, Dupont R, Frost J, Gaudilliere B, MacKenzie ET, Rousseau J, Scatton B, Wick A (1988) Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. J Pharmacology and Experimental Therapeutics 247(3):1211–1221Google Scholar
  45. Grinstein S, Rothstein A (1986) Mechanisms of regulation of the Na + /H + exchanger: topical review. J Membrane Biol 90:1–12Google Scholar
  46. Grinstein S, Cohen S, Rothstein A (1984) Cytoplasmic pH regulation in thymic lymphocytes by an amiloride-sensitive Na+/H+ antiport. J Gen Physiol 83:341–369PubMedGoogle Scholar
  47. Hachinski V, Norris JW (1985) The acute stroke. FA Davis Company, PhiladelphiaGoogle Scholar
  48. Hall ED, Pazara KE, Braughler JM (1988) 21-Aminosteroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils. Stroke 19:997–1002PubMedGoogle Scholar
  49. Halliwell B (1987) Oxidants and human disease: some new concepts. FASEB J 1:358–364PubMedGoogle Scholar
  50. Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. TINS 8:22–26Google Scholar
  51. Hansen AJ (1985) Effects of anoxia on ion distribution in the brain. Physiol Rev 65:101–148PubMedGoogle Scholar
  52. Hansford RG (1985) Relation between mitochondrial calcium transport and control of energy metabolism. Rev Physiol Biochem Pharmacol 102:1–72PubMedGoogle Scholar
  53. Harris RJ, Symon L (1984) Extracellular pH, potassium, and calcium activities in progressive ischaemia rat cortex. J Cereb Blood Flow Metab 4:178–186PubMedGoogle Scholar
  54. Harris RJ, Symon L, Branston NM, Bayhan M (1981) Changes in extracellular calcium activity in cerebral ischaemia. J Cereb Blood Flow Metab 1:203–209PubMedGoogle Scholar
  55. Hillered L, Ernster L, Siesjö BK (1984) Influence of in vitro lactic acidosis and hypercapnia on respiratory activity of isolated rat brain mitochondria. J Cereb Blood Flow Metab 4:430–437PubMedGoogle Scholar
  56. Hochachka PW, Mommsen TP (1983) Protons and anaerobiosis. Science 219:1391–1397PubMedGoogle Scholar
  57. Hossmann K-A (1985) Post-ischemic resuscitation of the brain: selective vulnerability versus global resistance. In: Kogure K, Hossmann K-A, Siesjö BK et al. (eds) Progress in brain research, vol 63. Elsevier, pp 3–17Google Scholar
  58. Jean T, Frelin C, Vigne P, Lazdunski M (1986) The Na + /H + exchange system in glial cell lines. Properties and activation by an hyperosmotic shock. Eur J Biochem 160(2):211–219PubMedGoogle Scholar
  59. Kaplan J, Dimlich RVW, Biros MH, Hedges J (1987) Mechanisms of ischemic cerebral injury. Resuscitation 15:149–158PubMedGoogle Scholar
  60. Komara JS, Nayini NR, Bialick HA, Indrieri RJ, Evans AT, Garritano AM, White BC, Aust SD (1986) Brain iron delocalization and lipid peroxidation following cardiac arrest. Ann Emerg Med 15:384–389PubMedGoogle Scholar
  61. Kraig RP, Chesler M (1989) Astrocytic acidosis in hyperglycemia and complete isch emia. J Cereb Blood Flow Metab (in press)Google Scholar
  62. Kraig RP, Pulsinelli WA, Plum F (1985) Hydrogen ion buffering during complete brain ischemia. Brain Res 342:281–290PubMedCentralPubMedGoogle Scholar
  63. Kraig RP, Pulsinelli WA, Plum F (1986) Carbonic acid buffer changes during complete brain ischemia. Am J Physiol 250 (Regulatory Integrative Comp Physiol 19):R348–R357PubMedCentralPubMedGoogle Scholar
  64. Kraig RP, Petito CK, Plum F, Pulsinelli WA (1987) Hydrogen ions kill brain at concentrations reached in ischemia. J Cereb Blood Flow Metab 7:379–386PubMedCentralPubMedGoogle Scholar
  65. Krause GS, White BC, Aust SD, Nayini NR, Kusum Kumar MBBS (1988) Brain cell death following ischemia and reperfusion: a proposed biochemical suquence. Crit Care Med 16:714-726PubMedGoogle Scholar
  66. Leonard JP, Salpeter MM (1979) Agonist-induced myopathy at the neuromuscular junction is mediated by calcium. J Cell Biol 82:811–819PubMedGoogle Scholar
  67. Ljunggren B, Schutz H, Siesjö BK (1974 a) Changes in energy state and acid-base parameters of the rat brain during complete compression ischemia. Brain Res 73:277–289PubMedGoogle Scholar
  68. Ljunggren B, Ratcheson RA, Siesjö BK (1974 b) Complete metabolic state following complete compression ischemia. Brain Res 73:291–307PubMedGoogle Scholar
  69. Ljunggren B, Norberg K, Siesjö BK (1974 c) Influence of tissue acidosis upon restitution of brain energy metabolism following total ischemia. Brain Res 77:173–186PubMedGoogle Scholar
  70. Lowry OH, Passonneau JV, Hasselberger FX, Schultz DW (1964) Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J Biol Chem 239:18–30PubMedGoogle Scholar
  71. MacDermott AB, Dale N (1987) Receptors, ion channels and synaptic potentials underlying the integrative actions of excitatory amino acids. TINS 10(7):280–284Google Scholar
  72. Mahnensmith RL, Aronsen PS (1985) The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res 57:773–788Google Scholar
  73. Martz D, Rayos G, Schielke GP, Betz AL (1989) Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in the rat. Stroke, in press -Google Scholar
  74. Mayer ML, Westbrook GL (1987) The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28:197–276PubMedGoogle Scholar
  75. McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. The New England Journal of Medicine 312(3):159–163PubMedGoogle Scholar
  76. Michelson AM, Jadot G, Puget K (1988) Treatment of brain trauma with liposomal Superoxide dismutase. Free Rad Res Comms 4(4):209–224Google Scholar
  77. Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52PubMedGoogle Scholar
  78. Mohamed AA, Gotoh O, Graham DI, Osborne KA, McCulloch JM, Mendelow AD, Teasdale GM, Harper AM (1985) Effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow and histopathology after middle cerebral artery occlusion. Ann Neurol 18:705–711PubMedGoogle Scholar
  79. Myers RE (1979 a) Lactic acid accumulation as cause of brain edema and cerebral necrosis resulting from oxygen deprivation. In: Korobkin R, Guilleminault G (eds) Advances in perinatal neurology. Spectrum, New York, pp 85–114Google Scholar
  80. Myers RE (1979 b) A unitary theory of causation of anoxic and hypoxic brain pathology. In: Fahn S, Davis JN, Rowland LP (eds) Cerebral hypoxia and its consequences. Adv Neurol 26, Raven Press, New YorkGoogle Scholar
  81. Nakayama H, Ginsberg MD, Dietrich WD (1988) Emopamil, a novel calcium channel blocker and serotonin S2 antagonist markedly reduces infarct size following middle cerebral artery occlusion in the rat. Neurology 38:1667–1673PubMedGoogle Scholar
  82. Nicholson C (1980) Dynamics of the brain cell microenvironment. Neurosci Res Pro gram Bull 18:177–322Google Scholar
  83. Nicotera P, Harzell P, Davis G, Orrenius S (1986) The formation of plasma membrane blebs in hepatocytes exposed to agents that increase cytosolic Ca 2 + is mediated by the activation of a non-lysosomal proteolytic system. FEBS Lett 209:139–144PubMedGoogle Scholar
  84. Nordström C-H, Siesjö BK (1978) Effects of phenobarbital in cerebral ischemia. Part I: Cerebral energy metabolism during pronounced incomplete ischemia. Stroke 9:327–335PubMedGoogle Scholar
  85. Olney J (1978) Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic as a tool in neurobiology. Raven Press, New York, pp 95–121Google Scholar
  86. Orrenius S, McConkey DJ, Jones DP, Nicotera P (1988) Ca2 +-activated mechanisms in toxicity and programmed cell death. ISI Atlas Sei: Pharmacology 2:319–324Google Scholar
  87. Oyzuart E, Graham DI, Woodruff GN, McCulloch J (1988) Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat. J Cereb Blood Flow Metab 8:138–143Google Scholar
  88. Park CK, Nehls DG, Graham DI, Teasdale GM, McCulloch J (1988) The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann Neurol 24:543–551PubMedGoogle Scholar
  89. Patt A, Harken AH, Burton LK, Rodell TC, Piermattei D, Schorr WJ, Parker NB, Berger EM, Horesh IR, Terada LS, Linas SL, Cheronis JC, Repine JE (1988) Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains. J Clin Invest 81:1556–1562PubMedCentralPubMedGoogle Scholar
  90. Plum F (1983) What causes infarction in ischemic brain? The Robert Wartenberg Lecture. Neurology 33:222–233PubMedGoogle Scholar
  91. Rasmussen H (1986) The calcium messenger system. N Engl J Med 314:1094–1101PubMedGoogle Scholar
  92. Rasmussen H, Waisman DM (1983) Modulation of cell function in the calcium messenger system. Rev Physiol Biochem Pharmacol 95:111–148Google Scholar
  93. Rehncrona S, Nielsen Hauge H, Siesjö BK (1989) Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: difference in effect by lactic acid and CO2. J Cereb Blood Flow Metab 9:65–70PubMedGoogle Scholar
  94. Reynolds IJ, Miller RJ (1988) Multiple sites for the regulation of the 7V-methyl-D-aspartate receptor. Mol Pharmacol 33:581–584PubMedGoogle Scholar
  95. Roos A, Boron WF (1981) Intracellular pH. Physiol Rev 61:296–434PubMedGoogle Scholar
  96. Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–111PubMedGoogle Scholar
  97. Rothman SM, Thurston JH, Hauhart RE (1987) Delayed neurotoxicity of excitatory amino acids in vitro. Neurosci 22(2):471–480Google Scholar
  98. Safar P (1986) Cerebral resuscitation after cardiac arrest: a review. Circulation 74 (suppl IV):138–153Google Scholar
  99. Salford LG, Plum F, Siesjö BK (1973) Graded hypoxia-oligemia in rat brain. I. Biochemical alterations and their implications. Arch Neurol 29:227–233PubMedGoogle Scholar
  100. Siesjö BK (1978) Brain energy metabolism. John Wiley, ChichesterGoogle Scholar
  101. Siesjö BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:155–185PubMedGoogle Scholar
  102. Siesjö BK (1984) Cerebral circulation and metabolism. J Neurosurg 60:883–908PubMedGoogle Scholar
  103. Siesjö BK (1985) Acid-base homeostasis in the brain: physiology, chemistry, and neurochemical pathology. In: Kongure K, Hossmann K-A, Siesjö BK, Welsh FA (eds) Progress in brain research. Elsevier Science Publishers B.V. (Biomedicial Division), vol 63, pp 121–154Google Scholar
  104. Siesjö BK (1988 a) Mechanisms of ischemic brain damage. Crit Care Med 16:954–963PubMedGoogle Scholar
  105. Siesjö BK (1988 b) Historical overview. Calcium, ischemia, and death of brain cells. Ann NY Acad Sci 522:638–661PubMedGoogle Scholar
  106. Siesjö BK (1988 c) Hypoglycemia, brain metabolism, and brain damage. Diabetes/Metabolism Reviews 4(2):113–144PubMedGoogle Scholar
  107. Siesjö BK (1988) Acidosis and ischemic brain damage. Neurochem Pathol 9:31–88PubMedGoogle Scholar
  108. Siesjö BK, Nilsson L (1971) The influence of arterial hypoxemia upon labile phosphates and upon extracellular and intracellular lactate and pyruvate concentration in the rat brain. Scand J Clin Lab Invest 27:83–96PubMedGoogle Scholar
  109. Siesjö BK, Wieloch T (1985) Cerebral metabolism in ischemia: neurochemical basis for therapy. Br J Anaesth 57:47–62PubMedGoogle Scholar
  110. Siesjö BK, Bengtsson F (1989) Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab. 9:127–140PubMedGoogle Scholar
  111. Siesjö BK, Bendek G, Koide T, Westerberg E, Wieloch T (1985) Influence of acidosis on lipid peroxidation in brain tissues in vitro. J Cereb Blood Flow Metab 5:253– 258PubMedGoogle Scholar
  112. Siesjö BK, Smith M-L, Warner DS (1987) Acidosis and ischemic brain damage. In: Raichle ME, Powers WJ (eds) Cerebrovascular diseases. Raven Press, New York, pp 83–95Google Scholar
  113. Siesjö BK, Bengtsson F, Grampp W, Theander S (1989) Calcium, excitotoxins and neuronal death in the brain. Ann NY Acad Sei, in pressGoogle Scholar
  114. Silvia RC, Piercey MF, Hoffmann WE, Chase RL, Braughler JM, Tang AH (1987) U-74006F, an inhibitor of lipid peroxidation, protects against lesion development following experimental stroke in the cat: histological and metabolic analysis. Soc Neurosci Abst 13:1495Google Scholar
  115. Smith M-L, van Hanwehr R, Siesjö BK (1986) Changes in extra-and intracellular pH in the brain during and following ischemia in hyperglycemic and in moderately hy-poglycemic rats. J Cereb Blood Flow Metabol 6:574–583Google Scholar
  116. Steen PA, Gisvold SE, Milde JH, Newberg LA, Scheithauer BW, Lanier WL, Michen-felder JD (1985) Nimodipine improves outcome when given after complete cerebral ischemia in primates. Anesthesiology 62:406–414PubMedGoogle Scholar
  117. Watkins JC, Olverman HJ (1987) Agonists and antagonists for excitatory amino acid receptors. TINS 10(7):265–272Google Scholar
  118. Westerberg E, Kehr J, Ungerstedt U, Wieloch T (1988) The NMDA-antagonist MK-801 reduces extracellular amino acid levels during hypoglycemia and prevents stria-tal damage. Neurosci Res Commun 3:151–158Google Scholar
  119. White BC, Hildebrand JF, Evans AT, Aronson L, Indrieri RJ, Hoehner T, Fox L, Huang R, Johns D (1985) Prolonged cardiac arrest and resuscitation in dogs: brain mitochondrial function with different artificial perfusion methods. Ann Emerg Med 14(5):383–388PubMedGoogle Scholar
  120. Wieloch T (1985) Hypoglycemia-induced neuronal damage is prevented by a N-methyl-D-aspartate receptor antagonist. Science 230:681–683PubMedGoogle Scholar
  121. Wieloch T, Harris RJ, Symon L, Siesjö BK (1984) Influence of severe hypoglycemia on brain extracellular calcium and potassium activities, energy and phospholipid metabolism. J Neurochem 43:160–168PubMedGoogle Scholar
  122. Wrogemann K, Pena SDJ (1976) Mitochondrial calcium overload: a general mecha nism for cell-necrosis in muscle diseases. Lancet I:672–674Google Scholar
  123. Young W, Wojak JC, DeCrescito V (1988) 21-Aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia. Stroke 19:1013–1019PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • B. K. Siesjö

There are no affiliations available

Personalised recommendations