title: Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke.
abstract: The potential benefit of 100 vol% normobaric oxygen (NBO) for the treatment of acute ischemic stroke patients is still a matter of debate. To advance this critical question, we studied the effects of intraischemic normobaric oxygen alone or in combination with recombinant tissue-plasminogen activator (rtPA) on cerebral blood flow and ischemic brain damage and swelling in a clinically relevant rat model of thromboembolic stroke. We show that NBO provides neuroprotection by achieving cerebral blood flow restoration equivalent to 0.9 mg/kg rtPA through probable direct interaction and facilitation of the fibrinolytic properties of endogenous tPA. In contrast, combined NBO and rtPA has no neuroprotective effect on ischemic brain damage despite producing cerebral blood flow restoration. These results 1) by providing a new mechanism of action of NBO highlight together with previous findings the way by which intraischemic NBO shows beneficial action; 2) suggest that NBO could be an efficient primary care therapeutic intervention for patients eligible for rtPA therapy; 3) indicate that NBO could be an interesting alternative for patients not eligible for rtPA therapy; and 4) caution the use of NBO in combination with rtPA in acute stroke patients.
authors.affiliation: Centre de Recherche, Centre Hospitalier Affilié Universitaire Hôtel-Dieu de Lévis, Lévis, Quebec, Canada.
authors.forename: H N
authors.initials: HN
authors.lastname: David
authors.forename: B
authors.initials: B
authors.lastname: Haelewyn
authors.forename: M
authors.initials: M
authors.lastname: Degoulet
authors.forename: D G
authors.initials: DG
authors.lastname: Colomb
authors.forename: J J
authors.initials: JJ
authors.lastname: Risso
authors.forename: J H
authors.initials: JH
authors.lastname: Abraini
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D013923:Thromboembolism / Q000188:drug therapy* / Q000378:metabolism; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D010100:Oxygen; D002118:Calcium