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NMDA receptor antagonism does not inhibit induction of ischemic tolerance in gerbil brainin vivo

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Abstract

Effects of high and moderate affinity uncompetitive NMDA receptor antagonists (+)MK-801 and memantine on ischemic tolerance were compared in relation to telemetrically controlled brain temperature. The tolerance to an injurious 3 min test of global forebrain ischemia in Mongolian gerbils was induced 48 h earlier by 2 min preconditioning ischemia. Normothermic preconditioning was virtually harmless, and greatly reduced neurode-generation evoked by test ischemia. In hyperther-mic animals it was injurious and failed to induce tolerance. Memantine (5 mg/kg) and (+)MK-801 (3 mg/kg) injected i.p. 1 h before preconditioning did not inhibit ischemic tolerance in the normo-thermic gerbils, while in hyperthermic animals treated with (+)MK-801 ischemic tolerance was partially restored. Subchronic 3 day infusion of memantine (30 mg/kg/day) significantly decreased neurodegeneration, and preconditioning in the nor-mothermic gerbils further reduced neuronal damage. Hyperthermia exacerbated preconditioning ischemia and in this way reduced expression of tolerance, while (+)MK-801 partially reversed this effect. Our results do not confirm previous reports on the role of NMDA receptors in the induction of ischemic tolerance in gerbils.

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Authors and Affiliations

  1. Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland

    Malgorzata Duszczyk, Apolonia Ziembowicz & Jerzy W. Lazarewicz

  2. Department of Neuropathology, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland

    Roman Gadamski

  3. Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt/M, Germany

    Wojciech Danysz

Authors
  1. Malgorzata Duszczyk
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  2. Roman Gadamski
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  3. Apolonia Ziembowicz
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  4. Wojciech Danysz
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  5. Jerzy W. Lazarewicz
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Correspondence to Jerzy W. Lazarewicz.

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Duszczyk, M., Gadamski, R., Ziembowicz, A. et al. NMDA receptor antagonism does not inhibit induction of ischemic tolerance in gerbil brainin vivo . neurotox res 7, 283–292 (2005). https://doi.org/10.1007/BF03033886

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  • DOI: https://doi.org/10.1007/BF03033886

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