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Ischemia as an Excitotoxic Lesion: Protection Against Hippocampal Nerve Cell Loss by Denervation

  • Conference paper
Mechanisms of Secondary Brain Damage

Part of the book series: Acta Neurochirurgica ((NEUROCHIRURGICA,volume 57))

Abstract

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers.

Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2–3 hours and of hippocampal pyramidal neurons after 2–3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect.

Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation.

Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models. If an immediately postischemic denervation of CA1 neurons is performed, there is a partly protection of these cells.

The GABA-ergic interneurons, which are lying among the pyramidal neurons in CA1 are always resistant to ischemia; receptor autoradiography indicates that they have glutamate receptors of the kainate/quisqualate type but no (or few) of the NMDA-type.

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Author information

Authors and Affiliations

  1. Cerebral Ischemia Research Group and Pharmabiotec Research Center, Institute of Neuropathology, University of Copenhagen, Denmark

    N. H. Diemer, F. F. Johansen, H. Benveniste, T. Bruhn, M. Berg, E. Valente & M. B. Jørgensen

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  1. N. H. Diemer
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  2. F. F. Johansen
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  3. H. Benveniste
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  4. T. Bruhn
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  6. E. Valente
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  7. M. B. Jørgensen
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Editors and Affiliations

  1. Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität, Klinikum Grosshadern, München, Federal Republic of Germany

    Alexander Baethmann

  2. Institut für Neurochirurgische Pathophysiologie, Johannes-Gutenberg-Universität, Mainz, Federal Republic of Germany

    Oliver Kempski

  3. Neurochirurgische Klinik, Ludwig-Maximilians-Universität, Klinikum Grosshadern, München, Federal Republic of Germany

    Ludwig Schürer

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© 1993 Springer-Verlag

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Diemer, N.H. et al. (1993). Ischemia as an Excitotoxic Lesion: Protection Against Hippocampal Nerve Cell Loss by Denervation. In: Baethmann, A., Kempski, O., Schürer, L. (eds) Mechanisms of Secondary Brain Damage. Acta Neurochirurgica, vol 57. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9266-5_14

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  • DOI: https://doi.org/10.1007/978-3-7091-9266-5_14

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