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PPAR Res. 2015;2015:246329. doi: 10.1155/2015/246329. Epub 2015 May 27.

PPAR-Alpha Agonist Used at the Acute Phase of Experimental Ischemic Stroke Reduces Occurrence of Thrombolysis-Induced Hemorrhage in Rats.

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1
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.
2
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.

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.

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