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Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-d-aspartate receptor antagonist MK-801

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Summary

FOS and JUN proteins are transcription factors thought to be involved in coupling neuronal excitation to target gene expression. Cortical infarction of consistent size and location was produced by irradiating the rat brain with Xenon light through the intact skull for 20 min following systemic injection of the photo-sensitizing dye, rose bengal. To investigate the time course and distribution pattern of five cellular ummediate early gene (IEG)-encoded proteins after focal ischemia, the expression of c-FOS, FOS B, c-JUN, JUN B and JUN D was studied immunocytochemically in sham-operated control animals and at different postischemic time intervals up to 24 h. A separate group of animals was pretreated with the non-competitive N-methyl-d-aspartate (NMDA) antagonist MK-801. Photochemically induced focal ischemia caused a rapid induction of FOS and JUN proteins in the entire ipsilateral cortex apart from the ischemic focus. Immunoreactivity in the ipsilateral subcortical gray and white matter and in the entire contralateral hemisphere was indistinguishable from control animals. Individual IEG-encoded proteins were sequentially induced with increased levels of immunoreactivity persisting for different time periods up to 24 h. c-FOS, FOS B, c-JUN and JUN B exhibited a characteristic distribution pattern as reflected by different staining intensities in individual cortical layers. The rapid IEG induction in the entire ipsilateral sensorimotor and limbic structure-associated cortices after photochemically induced infarction most likely reflects spreading depression caused by ischemia and mediated by NMDA receptors. This conclusion is supported by the finding that MK-801 pretreatment completely prevented the postischemic induction of FOS proteins and markedly attenuated the levels of JUN immunoreactivity in all cortical regions except in the peri-infarct area.

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Authors and Affiliations

  1. Department of Neuropathology, University of Heidelberg, Im Neuenheimer Feld 220, W-6900, Heidelberg, Federal Republic of Germany

    P. Gass, P. Köck & M. Kiessling

  2. Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 220, W-6900, Heidelberg, Federal Republic of Germany

    M. Spranger & W. Hacke

  3. Department of Physiology, University of Heidelberg, Im Neuenheimer Feld 220, W-6900, Heidelberg, Federal Republic of Germany

    T. Herdegen

  4. Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA

    R. Bravo

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Gass, P., Spranger, M., Herdegen, T. et al. Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-d-aspartate receptor antagonist MK-801. Acta Neuropathol 84, 545–553 (1992). https://doi.org/10.1007/BF00304474

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