title: PPAR-Alpha Agonist Used at the Acute Phase of Experimental Ischemic Stroke Reduces Occurrence of Thrombolysis-Induced Hemorrhage in Rats.
abstract: The impact of fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-α) agonist, on the risk of thrombolysis-induced hemorrhage during the acute phase of stroke in a rat model of stroke was studied. One-hour middle cerebral artery occlusion followed by thrombolysis with tissue plasminogen activator was made in rats receiving either fenofibrate or vehicle for 72 h after stroke. Evaluation of infarct, hemorrhage, middle cerebral artery vasoreactivity, and immunochemistry (CD11b for microglial activation, myeloperoxidase, and ICAM-1 for neutrophil infiltration) was performed. The PPAR-alpha agonist significantly reduced the risk of hemorrhage after thrombolysis in parallel with a decrease in the infarct volume and in the stroke-induced vascular endothelial dysfunction. These effects are concomitant with a reduction in microglial activation and neutrophil infiltration in infarct area. Our results strengthen the idea that using drugs such as fenofibrate, with pleiotropic properties due to PPAR-alpha agonism, may be of value to reduce thrombolysis-induced hemorrhage during acute stroke.
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Thavarak
authors.initials: T
authors.lastname: Ouk
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Maud
authors.identifier: 0000-0001-7024-8683
authors.initials: M
authors.lastname: Pétrault
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France ; University d'Artois, 62307 Lens, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pétrault
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France ; University d'Artois, 62307 Lens, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bérézowski
authors.affiliation: U1171, Departement de Pharmacologie Medicale, University Lille Nord de France, Faculté de Médecine, CHU Lille, 1 Place de Verdun, 59037 Lille Cedex, France ; Faculté de Médecine, Université de Lille 2, Lille, France ; Centre Hospitalier Universitaire, Lille, France ; Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet