Neurotoxicity Research

, 7:283 | Cite as

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

  • Malgorzata Duszczyk
  • Roman Gadamski
  • Apolonia Ziembowicz
  • Wojciech Danysz
  • Jerzy W. Lazarewicz


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.


Brain temperature Ischemic tolerance (+)MK-801 Neuroprotection Preconditioning Telemetry 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Malgorzata Duszczyk
    • 1
  • Roman Gadamski
    • 2
  • Apolonia Ziembowicz
    • 1
  • Wojciech Danysz
    • 3
  • Jerzy W. Lazarewicz
    • 1
  1. 1.Department of NeurochemistryMedical Research Centre, Polish Academy of SciencesWarsawPoland
  2. 2.Department of NeuropathologyMedical Research Centre, Polish Academy of SciencesWarsawPoland
  3. 3.Merz Pharmaceuticals GmbHFrankfurt/MGermany

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