title: Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-D-aspartate glutamate receptors improves hemorrhagic stroke outcome.
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.
authors.affiliation: Inserm UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, University Caen Lower-Normandy, Boulevard Becquerel, Caen, France. thomas.gaberel@hotmail.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Gaberel
authors.forename: Richard
authors.initials: R
authors.lastname: Macrez
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
authors.forename: Axel
authors.initials: A
authors.lastname: Montagne
authors.forename: Marie
authors.initials: M
authors.lastname: Hebert
authors.forename: Karl-Uwe
authors.initials: KU
authors.lastname: Petersen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Touze
authors.forename: Véronique
authors.initials: V
authors.lastname: Agin
authors.forename: Evelyne
authors.initials: E
authors.lastname: Emery
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods*; D020300:Intracranial Hemorrhages / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D008297:Male; D051379:Mice; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020521:Stroke / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D016194:Receptors, N-Methyl-D-Aspartate; D010959:Tissue Plasminogen Activator