Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-D-aspartate glutamate receptors improves hemorrhagic stroke outcome

Thomas Gaberel, Richard Macrez, Maxime Gauberti, Axel Montagne, Marie Hebert, Karl-Uwe Petersen, Emmanuel Touze, Véronique Agin, Evelyne Emery, Carine Ali, Denis Vivien

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro-neurotoxic effect of endogenous tissue plasminogen activator (tPA) via N-methyl-d-Aspartate (NMDA) receptors. Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy (αATD-GluN1 antibody) preventing the interaction of tPA with NMDA receptors. We found that a single intravenous injection of αATD-GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume.

Original languageEnglish
Pages (from-to)267-71
Number of pages5
JournalNeuropharmacology
Volume67
DOIs
Publication statusPublished - Apr 2013

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Antibodies, Monoclonal, Murine-Derived/administration & dosage
  • Immunotherapy/methods
  • Intracranial Hemorrhages/immunology
  • Male
  • Mice
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate/metabolism
  • Stroke/immunology
  • Tissue Plasminogen Activator/antagonists & inhibitors
  • Treatment Outcome

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