Glutamate Neurotoxicity and Effect of Antagonists —In Vitro Study using Hippocampal Neurons Exposed to Hypoxia

  • Eiji Kohmura
  • Kazuo Yamada
  • Akira Kinoshita
  • Toru Hayakawa

Abstract

Roles of glutamate in various pathological situations are suggested, though it is an physiological neurotransmitter. Studies using in vivo microdialysis technique showed rapid increase of extracellular glutamate concentration during the ischemic period in models of transient global ischemia, but it declined also rapidly after recirculation (Benveniste et al., 1984; Hagberg et al., 1985). Therefore slowly ongoing neuronal injury such as delayed neuronal loss is difficultly explained by elevated glutamate concentration during the ischemic period. We speculated that neurons might become more vulnerable to glutamate after exposure to ischemia and they might be thereafter injured by lower amount of glutamate. We intended to evaluate possible changes of glutamate neurotoxicity induced by subcritical hypoxia in vitro. We indeed confirmed increased sensitivity to glutamate after subcritical hypoxia(Kohmura et al., 1990). In this paper specific agonists and antagonists for the glutamate receptor subtypes were tested in order to evaluate the underlying mechanism.

Keywords

Toxicity Magnesium Depression Ischemia Selenium 

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References

  1. Benveniste H., Drejer J., Schousboe A., 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: 1369–1374PubMedCrossRefGoogle Scholar
  2. Hagberg H., Lehmann A., Sandberg M., Nystrom B., Jacobson I., Hamberger A. (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra-to extracellular compartments. J Cereb Blood Flow Metab 5:413–419PubMedCrossRefGoogle Scholar
  3. Kinoshita A., Yamada K., Hayakawa T. (1990) Hypoxic injury of rat cortical neurons in primary cell cultures. Exp Cell Biol 57:310–314Google Scholar
  4. Kohmura E., Yamada K., Hayakawa T., Kinoshita A., Matsumoto K., Mogami H. (1990) Hippocampal neurons become more vulnerable tp glutamate after subcritical hypoxia: an in vitro study. J Cereb Blood Flow Metab 10:877–884PubMedCrossRefGoogle Scholar
  5. Mayer M.L., Westbrook G.L., Guthrie P.B. (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurons. Nature 309:261–263PubMedCrossRefGoogle Scholar
  6. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. (1984) Magnesium gates glutamate-activated channels in mouse central neurons. Nature 307:452–465CrossRefGoogle Scholar
  7. Sheardown M.J., Nielsen E.∅., Hansen A.J., Jacobsen P., Honoré T. (1990) 2,3–Dihydroxy–6–nitro–7–sulfamoyl–benzo (F) quinoxaline: a neuroprotectant for cerebral ischemia. Science 247:571–574PubMedCrossRefGoogle Scholar
  8. Siesjö B.K., 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: 127–140PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Eiji Kohmura
    • 1
  • Kazuo Yamada
    • 1
  • Akira Kinoshita
    • 1
  • Toru Hayakawa
    • 1
  1. 1.Department of NeurosurgeryOsaka University Medical School,Fukushimaku, Osaka 553Japan

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