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Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms

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Abstract

A reduced blood or oxygen supply to the brain leads to neuronal death caused by excessive activation of glutamate receptors. Recent evidence suggests that two distinct phases of glutamate release produce this death. During ischaemia or hypoxia, glutamate is released by reversed operation of glutamate uptake carriers. It activates N-methyl-d-aspartate (NMDA) receptors, increases the intracellular concentration of Ca2+, and triggers a long-lasting potentiation of NMDA-receptor-gated currents. After ischaemia, glutamate released by Ca2+-dependent exocytosis activates an excessive influx of Ca2+ largely through potentiated NMDA-receptor-channels, which leads to neuronal death. The therapeutic implications of such a scheme are discussed.

References (69)

  • D. Nicholls et al.

    Trends Pharmacol. Sci.

    (1990)
  • R. Gill et al.

    Neuroscience

    (1988)
  • M. Tymianski

    Neuron

    (1993)
  • S.M. Rothman et al.

    Trends Neurosci.

    (1987)
  • B. Halliwell et al.

    Trends Neurosci.

    (1985)
  • J.P. Nowicki et al.

    Eur. J. Pharmacol.

    (1991)
  • Y. Katayama

    Brain Res.

    (1991)
  • M. Ikeda et al.

    Neurosci. Lett.

    (1989)
  • D. Lobner et al.

    Neurosci. Lett.

    (1990)
  • D. Attwell et al.

    Neuron

    (1993)
  • R.A. Kauppinen et al.

    Neuroscience

    (1988)
  • S. Miyazaki

    Brain Res.

    (1993)
  • N. Hori et al.

    Exp. Neurol.

    (1991)
  • Y. Bessho et al.

    Neuron

    (1994)
  • M.Y-T. Globus et al.

    Neurosci. Lett.

    (1991)
  • H. Monyer et al.

    Neuron

    (1994)
  • L. Chen et al.

    Neuron

    (1991)
  • Y. Katayama et al.

    Brain Res.

    (1992)
  • P. Schaeffer et al.

    Brain Res.

    (1991)
  • S. Zini et al.

    Neurosci. Lett.

    (1993)
  • M.P. Goldberg et al.

    Neurosci. Lett.

    (1988)
  • B.S. Meldrum

    Brain Res.

    (1992)
  • C.P. Taylor

    Trends Neurosci.

    (1993)
  • A. Rami et al.

    Brain Res.

    (1993)
  • B. Cheng et al.

    Neuron

    (1991)
  • G. Rordorf et al.

    Neuron

    (1991)
  • M.D. Taylor et al.

    Brain Res.

    (1985)
  • B.K. Siesjö

    News Physiol. Sci.

    (1990)
  • H. Hagberg

    J. Cereb. Blood Flow Metab.

    (1985)
  • I.A. Silver et al.

    J. Gen. Physiol.

    (1990)
  • I.A. Silver et al.

    J. Cereb. Blood Flow Metab.

    (1992)
  • C. Jiang et al.

    J. Physiol.

    (1992)
  • M. Bouvier et al.

    Nature

    (1992)
  • D.W. Choi et al.

    J. Neurosci.

    (1987)
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