Advertisement

Animal Models of Brain Hypoxia

  • Gary E. Gibson
  • Hsueh-Meei Huang
Part of the Neuromethods book series (NM, volume 22)

Abstract

Hypoxia (i.e., reduced oxygen availability) is a classical model of the metabolic encephalopathies or delirium. An understanding of how hypoxia alters brain function has implications for understanding other metabolic encephalopathies as well as aging and age-related disorders, such as Alzheimer’s disease. Utilizing a variety of models of hypoxia is necessary to determine the effects of hypoxia on brain function and to test hypotheses about the underlying mechanisms of its actions. Both in vivo and in vitro models of hypoxia are produced by either limiting the oxygen availability or impairing the tissues′ ability to utilize oxygen. The results demonstrate that the synthesis and release of neurotransmitters are particularly sensitive to hypoxia. The release of acetylcholine is diminished, whereas the release of dopamine and glutamate is accelerated. We postulate that diminished acetylcholine release impairs mental function, whereas the excessive release of dopamine and glutamate damages cells postsynaptically. Fundamental alterations in calcium homeostasis, particularly the ability of mitochondria to buffer calcium, appear to underlie these deficits. Furthermore, these changes in calcium appear to affect other second messenger systems, including an acceleration of the phosphatidylinositol cascade

Keywords

Brain Slice Thiamine Deficiency Potassium Cyanide Maple Syrup Urine Disease Adenylate Energy Charge 
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.

References

  1. Bachelard H. S., Lewis L. D., Ponten U., and Siesjo B. K. (1974) Mechanisms activating glycolysis in the brain in arterial hypoxia. J. Neurochem. 22, 395–401.PubMedGoogle Scholar
  2. Barclay L. L, Gibson G. E., and Blass J. P. (1981) Impairment of behavior and acetylcholine metabolism in thiamine deficiency. J. Pharmacol. Exp. Ther. 217, 537–543.PubMedGoogle Scholar
  3. Berkson H. (1966) Physiological adjustments to prolonged diving in the pacific green turtle (Chelonia agassizii). Comp. Biochem. Physiol. 18, 101–119.PubMedGoogle Scholar
  4. Boismare F., LePoncin M., Belliard J. P., and Hacpille L. (1975) Reduction of hypoxia induced disturbances by previous treatment with benserazide and L-Dopa in rats. Experientia 31, 1190–1192.PubMedGoogle Scholar
  5. Boismare F., LePoncin-Lafitte M., and Rapin J. R. (1979a) Blockade of the different enzymatic steps in the synthesis of brain amines and memory (CAR) in hypobaric hypoxic rats treated or not with L-DOPA, in,: Cat-echolamines: Basic and Clinical Frontiers (Usdin E., Kopin I. J., and Barchas J., eds.). Pergamon Press, New York, pp. 1726–1728.Google Scholar
  6. Boismare F., Saligaut G, Moore N., and LeClerc J. L (1979b) Avoidance learning and mechanisms of protective effect of apomorphine under hypoxia. Acta Neurol. Scand. 60, 160,161.Google Scholar
  7. Booth R. F. G. and Clark J. B. (1978) A rapid method for the preparation of relatively pure metabolically competent synaptosomes from rat brain. Biochem. J. 176, 365–370.PubMedGoogle Scholar
  8. Booth R. F. G., Harvey S. A. K., and Clark J. B. (1983) Effects of in vivo hypoxia on acetylcholine synthesis by rat brain synaptosomes. J. Neurochem. 40, 106–110.PubMedGoogle Scholar
  9. Broderick P. A. and Gibson G. E. (1989) Dopamine and serotonin in rat striatum during in vivo hypoxic-hypoxia. Metab. Brain Dis. 4, 143–153.PubMedGoogle Scholar
  10. Brown R. M., Davis J. N., and Carlsson A. (1973) Dopa reversal of hypoxic-induced disruption of the conditioned avoidance response. J. Pharm Pharmacol. 25, 412–414.PubMedGoogle Scholar
  11. Brown R. M., Davis J. N., and Carlsson A. (1974) Changes in biogenic amine synthesis and turnover induced by hypoxia and/or foot shock stress II. The central nervous system. J. Neural. Transm. 35, 293–305.PubMedGoogle Scholar
  12. Brown R. M., Kehr W., and Carlsson A. (1975) Functional and biochemical aspects of catecholamine metabolism in brain under hypoxia. Brain Res. 85, 491–509.PubMedGoogle Scholar
  13. Carroll J. M., Toral-Barza L., Joh T., and Gibson G. E. (1990) The effects of glucose and oxygen deprivation on the responses of c-fos and cytosolic free calcium to K+-stimulation in PC-12 cells. J. Cell Biol. 115, 307a.Google Scholar
  14. Chih C. P., Feng Z. C., Rosenthal M., Lutz P. L., and Sick T. J. (1989) Energy metabolism, ion homeostasis, and evoked potentials in anoxic turtle brain. Am. J. Physiol. 257, R854–R860.PubMedGoogle Scholar
  15. Choi D. W. (1990) Cerebral hypoxia-some new approaches and unanswered questions. J. Neurosci. 10, 2493–2501.PubMedGoogle Scholar
  16. Dagani F., Feletti F., and Canevari L. (1989) Effects of diltiazem on bioenergetics, K+ gradients, and free cytosolic Ca-2+ levels in rat brain synaptosomes. J. Neurochem. 53, 1379–1389.PubMedGoogle Scholar
  17. Davis J. N. and Carlsson A. (1973) Effect of hypoxia on tyrosine and tryptophan hydroxylation in unanesthetized rat brain. J. Neurochem. 20, 913–915.PubMedGoogle Scholar
  18. Deshmuhk D. R., Owen O E, and Patel M. S. (1980) Effect of aging on the metabolism of pyruvate and 3-hydroxybutyrate in nonsynaptic and synaptic mitochondria from rat brain. J. Neurochem. 34, 1219–1224.Google Scholar
  19. Dienel G., Ryder E., and Greengard O. (1977). Distribution of mitochon-drial enzymes between the perikaryal and synaptic fractions of immature and adult rat brain. Biochim. Biophys. Acta. 496, 484–494.PubMedGoogle Scholar
  20. Dodge P. W. and Takemori A. E. (1972) Effects of morphine, nalorphine and pentobarbital alone and in combinations on cerebral glycolytic substrates and cofactors of rat in vivo. Biochem. Pharmacol. 21, 287–294.PubMedGoogle Scholar
  21. Duan J. M. and Karmazyn M. (1989) Acute effects of hypoxia and phosphate on two populations of heart mitochondria. Mol. Cell. Biochem. 90, 47–56PubMedGoogle Scholar
  22. Duffy T. E., Kohle S. J., and Vannucci R. (1975) Carbohydrate and energy metabolism in perinatal rat brain: Relation to survival in anoxia. J. Neurochem. 24, 271–276.PubMedGoogle Scholar
  23. Duffy T. E., Nelson S. R, and Lowry O. H. (1972) Cerebral carbohydrate metabolism during acute hypoxia and recovery. J. Neurochem. 19, 959–977.PubMedGoogle Scholar
  24. Dunkley P. R., Rostas J. A. P., Heath J. W., and Powis D. A. (1987) In vitro methods for studying secretion, in The Secretory Process, vol. 3 (Poisner A. and Trifaro J. M., eds.) Elsevier, New York, pp. 315–334.Google Scholar
  25. Eyer P., Kiese M., Lipowsky G., and Weger N. (1974) Reactions of 4-dimethylaminophenol with hemoglobin, and autoxidation of 4-dimethylaminophenol. Chem. Biol. Interact. 8, 41–59.PubMedGoogle Scholar
  26. Freeman G. B. and Gibson G. E. (1984) Stress indices in blood in animals restrained for focussed microwave radiation. Fed. Proc. 43, 772.Google Scholar
  27. Freeman G. B. and Gibson G. E. (1986) Effect of decreased oxygen on in vitro release of endogenous 3,4-dihydroxphenylethylamine from mouse striatum. J. Neurochem. 47, 1924–1931.PubMedGoogle Scholar
  28. Freeman G. B., Mykytyn V., and Gibson G. E. (1987) Differential alteration of dopamine, acetylcholine and glutamate release during anoxia and/ or 3,4-diaminopyridine treatment. Neurochem. Res. 12, 1019–1027.PubMedGoogle Scholar
  29. Freeman G. B., Nielsen P., and Gibson G. E. (1986a) Monoamine neurotransmitter metabolism and locomotor activity during chemical hypoxia. J. Neurochem. 46, 733–738.PubMedGoogle Scholar
  30. Freeman G. B., Nielsen P., and Gibson G. E. (1986b) Behavioral and neuro-chemical interactions of morphine and hypoxia. Pharmacol. Biochem. Behav. 24, 1687–1693.PubMedGoogle Scholar
  31. Fujii T., Hayashi M., Toita K, and Yamasaki Y. (1990) Effects of coenzymes Q2 and Q10 on the field potential of guinea pig olfactory cortex slices maintained in hypoxia. Neurosci. Lett. 110, 40–45.PubMedGoogle Scholar
  32. Gibson G. E. (1985) Hypoxia, in, Cerebral Energy Metabolism and Metabolic Encephalopathy. (McCandless D. W., ed.), Plenum, New York, pp. 43–78.Google Scholar
  33. Gibson G. E., Barclay L. L., and Blass J. P. (1982) The role of the cholinergic system in thiamin deficiency in, Thiamin: Twenty Years of Progress (Sable H. Z. and Gubler C. J., eds.), Ann. NY Acad. Sci 378, 382–403.Google Scholar
  34. Gibson G. E. and Blass J. P. (1976a) Impaired synthesis of acetylcholine in brain accompanying hypoglycemia and mild hypoxia. J. Neurochem. 27, 37–42.PubMedGoogle Scholar
  35. Gibson G. E. and Blass J. P. (1976b) Inhibition of acetylcholine synthesis and carbohydrate utilization by Maple-Syrup-Urine Disease metabolites. J. Neurochem 26, 1073–1078.PubMedGoogle Scholar
  36. Gibson G. E. and Blass J. P. (1976c) A relation between [NAD+]/[NADH] potential and glucose utilization in rat brain slices. J. Biol. Chem. 25, 4127–4130.Google Scholar
  37. Gibson G. E. and Duffy T. E. (1981) Impaired synthesis of acetylcholine by mild hypoxic hypoxia or nitrous oxide. J. Neurochem. 36, 28–33.PubMedGoogle Scholar
  38. Gibson G. E., Freeman G. B., Broderick P., and Nielsen P. (1987) Possible calcium-mediated events in selective vulnerability. Proc. XIII Int. Symposium on Cereb. Blood Flow and Metabolism 7S, 155.Google Scholar
  39. Gibson G. E., Freeman G. B., and Mykytyn V. (1988) Selective damage in striatum and hippocampus with in vitro anoxia. Neurochem. Res. 13, 329–335.PubMedGoogle Scholar
  40. Gibson G. E., Jope R., and Blass J. P. (1975) Decreased synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces. Biochem. J. 148, 17–23.PubMedGoogle Scholar
  41. Gibson G. E., Manger T., Toral-Barza L., and Freeman G. (1989) Cytosolic free calcium and neurotransmitter release with decreased availability of glucose or oxygen. Neurochem. Res. 14, 437–443.PubMedGoogle Scholar
  42. Gibson G. E. and Mykytyn V. (1988) An in vitro model of anoxic-induced damage in mouse brain. Neurochem. Res. 13, 9–20.PubMedGoogle Scholar
  43. Gibson G. E., Nielsen P., Mykytyn V., Carlson K., and Blass J. P. (1989) Regionally selective alterations in enzymatic activities and metabolic fluxes during thiamin deficiency. Neurochem. Res. 14, 17–24.PubMedGoogle Scholar
  44. Gibson G. E., Pelmas C. J., and Peterson C. (1983) Cholinergic drugs and 4-aminopyridine alter hypoxic-induced behavioral deficits. Pharmacol. Biochem. Behav. 18, 909–916.PubMedGoogle Scholar
  45. Gibson G. E. and Peterson C. (1983) Acetylcholine metabolism in septum and hippocampus in vitro. J. Biol. Chem. 258, 1142–1145.PubMedGoogle Scholar
  46. Gibson G. E. and Peterson C. (1987) Calcium and the aging nervous system. Neurobiol. Aging 8, 329–343.PubMedGoogle Scholar
  47. Gibson G. E. and Peterson C. (1982) Decreases in the release of acetylcholine in vitro with low oxygen. Biochem. Pharmacol. 31, 111–115.PubMedGoogle Scholar
  48. Gibson G. E. and Peterson C. (1984) Pharmacological approaches to age-related deficits in oxidative metabolism. Assessment in Geriatric Psy-chopharmacology, (Crook T., Ferris S., and Bartus R., eds.), Mark Powley Assoc. Inc., New Canaan, CT, pp. 323–343.Google Scholar
  49. Gibson G. E., Peterson G, and Sansone, J. (1981a) Decreases in amino acid and acetylcholine metabolism during hypoxia. J. Neurochem. 37, 192–201.PubMedGoogle Scholar
  50. Gibson G. E., Peterson C., and Sansone J. (1981b) Neurotransmitter and carbohydrate metabolism during aging and mild hypoxia. Neurobiol Aging 2, 165–172.PubMedGoogle Scholar
  51. Gibson G. E., Shimada M., and Blass, J. P. (1978) Alterations in acetylcholine synthesis and in cyclic-GMP in mild cerebral hypoxia. J. Neurochem. 31, 757–760.PubMedGoogle Scholar
  52. Gibson G. E., Shimada M., and Blass J. P. (1979) Protection by Tris(hydroxymethyl)aminomethane against behavioral and neuro-chemical effects of hypoxia. Biochem. Pharmacol. 28, 167–174.Google Scholar
  53. Gibson G. E., Toral-Barza L., and Huang H.-M. (1991) Cytosolic free calcium in synaptosomes during hypoxia. Neurochem. Res. 16, 461–467.PubMedGoogle Scholar
  54. Gibson G. E., Toral-Barza L., Manger T., and Freeman G. (1988) Neurotrans-mitters and calcium during hypoxia, in, Cerebral Ischemia and Calcium (Hartman A. and Kuschinsky W., eds.), Springer-Verlag, New York pp. 215–222.Google Scholar
  55. Glass H. G., Snyder, F. F., and Webster, R. (1944) The rate of decline in resistance to anoxia of rabbits, dogs and guinea pigs from the onset of viability to adult life. Am. J. Physiol. 140, 609–615.Google Scholar
  56. Griffiths T., Evans M. C., and Meldrum B. S. (1983) Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allylglycine. Neurosci. 10, 385–389.Google Scholar
  57. Gurdjian E. S., Stone W. E., and Webster J. E. (1944) Cerebral metabolism in hypoxia. Arch. Neurol. Psychiatr. 51, 472–477.Google Scholar
  58. Haldane J. S., Kellas A. M., and Kennaway, E. L. (1919) Experiments on acclimatization to reduced atmospheric pressure. J. Physiol. (Lond.) 53, 181.Google Scholar
  59. Hansen A. J. (1985) Effect of anoxia on ion distribution in the brain. Physiol. Rev. 65, 101–148.PubMedGoogle Scholar
  60. Hirsch J. A. and Gibson G. E. (1984a) Selective alteration of neurotransmitter release by low oxygen in vitro. Neurochem. Res. 9, 1039–1049.PubMedGoogle Scholar
  61. Hirsch J. A. and Gibson G. E. (1984b) Thiamine antagonists and the release of acetylcholine and norepinephrine from brain slices. Biochem. Pharmacol. 33, 2325–2327.PubMedGoogle Scholar
  62. Huang H.-M. and Gibson G. E. (1989a) Phosphahdylinositol metabolism during in vitro hypoxia. J. Neurochem. 52, 830–835.PubMedGoogle Scholar
  63. Huang H.-M. and Gibson G. E. (1989b) Effects of in vitro hypoxia on depolarization-stimulated accumulation of inositol phosphates in synaptosomes. Life Sci. 45, 1443–1449.PubMedGoogle Scholar
  64. Kass I. S. and Lipton P. (1982) Mechanisms involved in irreversible anoxic damage to the in vitro rat hippocampal slice. J. Physiol. 332, 459–472.PubMedGoogle Scholar
  65. Kauppinen R. A. and Nicholls D. G. (1986) Failure to maintain glycolysis in anoxic nerve terminals. J. Neurochem. 47, 1864–1869.PubMedGoogle Scholar
  66. Kawasaki K., Traynelis S. F., and Dingledine R. (1990) Different responses to CA1 and CA3 regions to hypoxia in rat hippocampal slice. J. Neurophysiol. 63, 385–394.PubMedGoogle Scholar
  67. Ksiezak H. and Gibson G. E. (1981a) Oxygen dependence on glucose and acetylcholine metabolism in slices and synaptosomes from rat brain. J. Neurochem. 37, 305–324.PubMedGoogle Scholar
  68. Ksiezak H. J. and Gibson G. E. (1981b) Acetylcholine synthesis and CO2 production from variously labelled glucose in rat brain slices and synaptosomes. J. Neurochem. 37, 88–94.PubMedGoogle Scholar
  69. Leahy T. and Smith R. (1960) Notes on methemoglobin determination. Clin. Chem. 6, 148–152.PubMedGoogle Scholar
  70. Lipowski Z. J. (1980) Delirium. Charles C. Thomas, New York.Google Scholar
  71. Lipowski Z. J. (1989) Delirium in the elderly patient. N. Engl. J. Med. 320, 578–582.PubMedGoogle Scholar
  72. Lipowski Z. J. (1987) Delirium (Acute Confusional States). J. Am. Med. Assoc. 258, 1789–1792.Google Scholar
  73. Lowry O. H. and Passonneau J. V. (1972) A Flexible System of Enzymatic Analysis, Academic Press, New York.Google Scholar
  74. Lutz B. R. and Schneider E. C. (1919) Alveolar air and respiratory volume at low oxygen tensions. Am. J. Physiol. 50, 280.Google Scholar
  75. Lutz P. L., Rosenthal M., and Sick T. J. (1985) Living without oxygen: Turtle brain as a model of anaerobic metabolism. Mol. Physiol. 8, 411–425.Google Scholar
  76. MacMillan V. (1975a) The effects of acute carbon monoxide intoxication on the cerebral energy metabolism of the rat. Can. J. Physiol. Pharmacol. 53, 354–362.PubMedGoogle Scholar
  77. MacMillan V. (1975b) Regional cerebral blood flow of the rat in acute carbon monoxide intoxication. Can. J. Physiol. Pharmacol. 53, 644–650.PubMedGoogle Scholar
  78. McFarland R. A. (1953) Stimuli primarily related to high altitude flight, in Human Factors in Our Transportation, McGraw-Hill, NY pp. 153–169.Google Scholar
  79. McFarland R. A. and Evans J. N. (1939) Alterations in dark adaptation under reduced oxygen tensions. Am. J. Physiol. 7, 37.Google Scholar
  80. McFarland R. A. and Forbes W. H. (1940) The effects of variation in the concentration of oxygen and of glucose on dark adaptation. J. Gen. Physiol. 24, 69.PubMedGoogle Scholar
  81. McFarland R. A., Roughton F. J. W., and Halperin M. H. (1944) The effects of CO2 and altitude on visual thresholds. J. Aviation Med. 15, 381–388.Google Scholar
  82. McIlwain H. and Bachelard H. S. (1971) Biochemisty and the Central Nervous System, 4th ed., Churchill Livingstone, Edinburgh and London.Google Scholar
  83. McIlwain H. and Bachelard H. S. (1985) Biochemisty and the Central Nervous System. 5th ed., Churchill Livingstone, New York.Google Scholar
  84. Miller A. L., Hawkins R. A., Harris R. L., and Veech R. L. (1972) The effects of acute and chronic morphine treatment and of morphine withdrawal on rat brain in vivo. J. Biochem. 129, 463–469.Google Scholar
  85. Myers R. E. (1979) A unitary theory of causation of anoxic and hypoxic brain pathology. Adv Neurol. 26, 195–213.PubMedGoogle Scholar
  86. Nielsen P. E. and Gibson G. E. (1986) Mitochondrial and plasma membrane potentials during anoxia and normoxia. Soc. Neurosci. Abstr. 12, 1403.Google Scholar
  87. Nishida T., Inoue T., Kamiike W., Kawashima Y., and Tagawa K. (1989) Involvement of Ca2+ release and activation of phospholipase-A2 in mitochondrial dysfunction during anoxia. J. Biochem. 106, 533–538.PubMedGoogle Scholar
  88. Parsons D. W. and Macmillan D. L (1990) The effect of carbon monoxide on the function of a crustacean sensory receptor is no different to the effect of hypoxia. Res Comm. Chem Path. Pharmacol. 67, 229–240.Google Scholar
  89. Peterson C. and Gibson G. E. (1982) 3,4-Diaminopyridine alters acetylcholine metabolism and behavior during hypoxia. J. Pharmacol. Exp. Ther. 222, 576–582.PubMedGoogle Scholar
  90. Peterson C. and Gibson G. E. (1984) Synaptosomal calcium metabolism during hypoxia and 3,4-diaminopyridine treatment. J. Neurochem. 42, 248–253.PubMedGoogle Scholar
  91. Peterson C., Gibson G. E., and Blass J. P. (1985a) Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer’s disease. N. Engl. J. Med. 312, 1063,1064.PubMedGoogle Scholar
  92. Peterson C., Nicholls D. G., and Gibson G. E. (1985b) Subsynaptosomal calcium distribution during hypoxia and 3,4-diaminopyridine treatment. J. Neurochem. 45, 1779–1790.PubMedGoogle Scholar
  93. Plum F. (1975) The metabolic encephalopathies. The Nervous System. Clin. Neurosci. 2, 193–201.Google Scholar
  94. Plum F. and Posner J. B. (1980) The Diagnosis of Stupor and Coma, 3rd Ed., F. A. Davis, Philadelphia, PA.Google Scholar
  95. Ponten U., Ratcheson R. A., Salford L. G. and Siesjo B. K (1973) Optimal freezing conditions for cerebral metabolites in rats. J. Neurochem. 21, 1127–1138.PubMedGoogle Scholar
  96. Rising C. L. and D′Alecy L. G. (1989) Hypoxia-induced increases in hypoxic tolerance augmented by beta-hydroxybutyrate in mice. Stroke 20, 1219–1225.PubMedGoogle Scholar
  97. Rothman S. M. (1983) Synaptic activity mediates death of hypoxic neurons. Science 220, 536,537.PubMedGoogle Scholar
  98. Saligaut C., Moore N., Boulu R., Plotkine M., LeClerc J. L., Prioux-Guyonneau M., and Boismare F. (1981) Hypobaric hypoxia: Central catecholamine levels and cortical PO2, and avoidance response in rats treated with apomorphine. Aviat. Space Environ. Med. 52, 166–170.PubMedGoogle Scholar
  99. Saligaut C., Moore N., Chretien P., Daoust M., Richard O., and Boismare, F. (1982). Interference between central dopaminergic stimulation and adrenal secretion in normoxic, hypobaric and hypoxic rats. Stroke 6, 859–864.Google Scholar
  100. Shimada K, Kihara T., Kurimoto K., and Watanaabe M. (1974). Incorporation of 14C from [U-14C]glucose into free amino acids in mouse brain regions under cyanide intoxication. J. Neurochem 23, 379–384.PubMedGoogle Scholar
  101. Siesjo B. K. (1981) Cell damage in the brain: a speculative synthesis. J. Cereb. Blood Flow Metab. 1, 155–185.PubMedGoogle Scholar
  102. Siesjo B. K. and Nilsson L. (1971) The influence of arterial hypoxemia upon labile phosphates and upon extracellular and intracellular lactate and pyruvate concentrations in the rat brain. Scand. J. Clin Lab. Invest. 27, 83–96PubMedGoogle Scholar
  103. Simon R. P., Griffiths R., Evans M. C., Swan J. J., and Meldrum B. S. (1984) Calcium overload in selectively vulnerable neurons of hippocampus during and after ischemia: An electron microscopy study in the rat. J. Cereb. Blood Flow Metab. 4, 350–361.PubMedGoogle Scholar
  104. Sims N. R. and Blass J. P. (1985) Expression of classical mitochondrial respiratory responses in homogenates of rat forebrain. J. Neurochem. 47, 496–505.Google Scholar
  105. Smith P. G., Slotkin T. A., and Mills, E. (1982) Development of sympathetic ganglionic neurotransmission in the neonatal rat. Pre-and postgangli-onic nerve response to asphyxia and 2-deoxyglucose. Neuroscience 7, 501–507.PubMedGoogle Scholar
  106. Stavinoha W. B., Weintraub S. T., and Modak A. T. (1973) The use of microwave heating to inactivate cholinesterase in the rat brain prior to analysis for acetylcholine. J. Neurochem. 20, 361–371.PubMedGoogle Scholar
  107. Sylvia A. L., Seidler F. J., and Slotkin T. A. (1989) Effect of transient hypoxia on oxygenation of the developing rat brain-Relationships among haemoglobin saturation, autoregulation of blood flow and mitochon-drial redox state. J Develop Physiol. 12, 287–292.Google Scholar
  108. Thom S. R. (1990) Carbon monoxide-mediated brain lipid peroxidation in the rat. J. Appl. Physiol. 68, 997–1003.PubMedGoogle Scholar
  109. Van Reempts J., Haseldonckx M., Van de Ven M., and Borgers M. (1984) Morphology and ultrastructural calcium distribution in the rat hippocampus after severe transient ischemia, in Cerebral Ischemia, (Bes A., Braquet P., Paoletti R., and Siesjo, eds.), Elsevier, NY, pp. 113–118.Google Scholar
  110. Veech R. L, Harris R. L, Veloso D., and Veech E. H. (1973) Freeze-blowing: A new technique for the study of brain in vivo. J. Neurochem. 20, 183–188.PubMedGoogle Scholar
  111. Vicario C., Juanes M. C., Martinbarrientos J., and Medina J. M. (1990) Effect of postnatal hypoxia on ammonia metabolism during the early neonatal period in the rat. Biol. Neonate 57, 119–125.PubMedGoogle Scholar
  112. Walz W. and Harold D. E. (1990) Brain lactic acidosis and synaptic function. Can. J. Physiol. Pharmacol. 68, 164–169.PubMedGoogle Scholar
  113. Wilson D. F., Erecinska M., Drown C., and Silver I. (1979) The oxygen dependence of cellular energy metabolism. Arch. Biochem. Biophys. 195, 485–493.PubMedGoogle Scholar
  114. Zeman E. M., Pearson C. I., and Brown J. M. (1990) Induction of hypoxia in glass versus permanox petri dishes. Radiation Res. 122, 72–76.PubMedGoogle Scholar

Copyright information

© The Humana Press Inc 1992

Authors and Affiliations

  • Gary E. Gibson
    • 1
  • Hsueh-Meei Huang
    • 1
  1. 1.Cornell University Medical CollegeWhite Plains

Personalised recommendations