Effect of fenofibrate on brain infarction, brain swelling and edema in focal-transient cerebral ischemia in rat

Increasing evidence has demonstrated that activation of peroxisome proliferator-activated receptor alpha (PPARα), which belongs to the nuclear receptor family of ligand-activated transcription factors, after cerebral ischemia exhibit neuroprotective functions including anti-oxidative, anti-apoptotic and anti-inflammatory effects. The aim of this study was to evaluate the pretreatment effects of PPARα agonist, fenofibrate, on brain infarction, tissue swelling, and brain edema in an experimental model of ischemic stroke.

The study included three groups of rats (N=36); sham, control ischemic, and treated ischemic groups. Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fenofibrate (200 mg/kg/day) by oral route for 4 days before induction of MCAO. Neurological deficit score (NDS), infarct volume (TTC staining method), tissue swelling, and brain edema were assessed 24 hours after termination of MCAO.

MCAO induced neurological dysfunction (2.83±0.16), brain infarction (282±30 mm3), brain swelling (15.13±2.29 %), and edema (17.23±1.97%) in the control ischemic group. Administration of fenofibrate in the treated ischemic rats significantly reduced neurological dysfunction (2.14±0.14), brain infarction (92±28 mm3), brain swelling (4.35±1.42%), and edema (5.49±1.44) compared to the rats in the control ischemic group.

Our findings indicated that activation of PPARα by a specific agonist, fenofibrate, effectively decreased the cerebral ischemia-reperfusion injuries as well as brain swelling and edema in an experimental model of ischemic stroke.