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

Neuropharmacology. 2013 Apr;67:267-71. doi: 10.1016/j.neuropharm.2012.11.023. Epub 2012 Dec 3.

Abstract

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.

MeSH terms

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

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Receptors, N-Methyl-D-Aspartate
  • Tissue Plasminogen Activator