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 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. © 2015 sophie gautier et al.