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Importance of Postischemic Neurotransmission in Delayed Neuronal Death

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Maturation Phenomenon in Cerebral Ischemia

Summary

Glutamatergic and noradrenergic neurotransmissions are important for the development of delayed neuronal death. Thus, neuronal damage in the rat hippocampus following transient cerebral ischemia and in the striatum following insulin-induced hypoglycemia is mitigated by pharmacological interventions in the postinsult period. Postischemic treatment with idazoxan, an a2-adrenoceptor antagonist and ligand at imidazole receptors, decreases delayed neuronal damage following transient cerebral ischemia. Blockade of one type of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor, diminishes neuronal necrosis when given after a period of hypoglycemia but not following transient severe cerebral ischemia. Following severe ischemia blockade of the glutamatergic ionotropic quisqualate (AMPA) receptor significantly diminishes neuronal damage. During and immediately following ischemia calcium ions and changes in membrane lipid composition and structure stimulate translocation of protein kinase C (PKC) from the cytosol to the cell membranes, while later in the reperfusion phase PKC is downregulated. This may lead to an enhanced AMPA receptor activation of voltage operated ion channels in the early reperfusion phase. Later, downregulation of PKC may lead to a decreased influence of trophic factors and loss of the inhibitory feedback mechanisms regulating glutamate receptor mediated inositol trisphosphate formation causing an abberant intracellular calcium ion homeostasis.

We propose that following moderate ischemia NMDA receptors mediate glutamate neurotoxicity in the postischemic phase, while following severe ischemia the AMPA receptors are more important. The noradrenaline system may be protective by antagonizing postischemic activation of AMPA receptors. We propose that glutamatergic neurotransmission becomes deleterious following ischemia due to transient activation and delayed degradation of protein kinases.

This work was supported by the Medical Faculty at Lund University, United States Public Health Services (grant no. NS 25302), the Swedish Medical Research Council (grant no. 8644), The Laerdal Foundation, and The Swedish Stroke Foundation.

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Authors
  1. T. Wieloch
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  2. K. Bergstedt
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  3. M. Cardell
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  4. I. Gustafson
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  5. T. Honoré
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  6. B. R. Hu
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  7. F. Boris-Möller
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  8. B. Nellgård
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  9. E. Westerberg
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, Musashino Red-Cross Hospital, 1-26-1, Kyonancho, Musashino-shi, Tokyo 180, Japan

    Umeo Ito M.D.

  2. Department of Neurosurgery, School of Medicine, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, Japan

    T. Kirino M.D.

  3. Department of Neuropathology, Medical Research Center, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan

    T. Kuroiwa M.D.

  4. Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Health, Bethesda, Maryland, USA

    Igor Klatzo M.D.

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© 1992 Springer-Verlag Berlin Heidelberg

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Wieloch, T. et al. (1992). Importance of Postischemic Neurotransmission in Delayed Neuronal Death. In: Ito, U., Kirino, T., Kuroiwa, T., Klatzo, I. (eds) Maturation Phenomenon in Cerebral Ischemia. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77134-7_12

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  • DOI: https://doi.org/10.1007/978-3-642-77134-7_12

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