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

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 plasmin...

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Bibliographic Details
Published in:PPAR Research 2015-01, Vol.2015 (2015), p.37-42
Main Authors: Bérézowski, Vincent, Pétrault, Olivier, Maud, Pétrault, Thavarak, Ouk, Gautier, Sophie, Bordet, Régis
Format: Article
Language:English
Subjects:
Animals
Drug dosages
Endothelium
Hemorrhage
Ischemia
Physiological aspects
Prevention
Rodents
Stroke
Stroke (Disease)
Transcription factors
Veins & arteries
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Summary: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.
ISSN:1687-4757
1687-4765
DOI:10.1155/2015/246329