Fenofibrate, a peroxisome proliferator-activated receptor α agonist, exerts neuroprotective effects in traumatic brain injury

Peroxisome proliferator-activated receptor alpha (PPAR alpha) has been demonstrated to reduce inflammation in various inflammatory diseases. As traumatic brain injury (TBI) caused a neuroinflammatory response, we examined the effect of fenofibrate, a PPAR alpha agonist, on the post-traumatic consequences caused by lateral fluid percussion of brain in rats. The effects of fenofibrate (50 and 100 mg/kg) were evaluated on the consequences of TBI in the early phase (6 and 24 h) and the late phase (7 days) after TBI. Neurological deficit, brain lesion, cerebral oedema and ICAM-1 expression were evaluated. Treatment with fenofibrate (given p.o. at 1 and 6h after TBI) decreases the neurological deficit induced by TBI at 24 h. Furthermore, fenofibrate reduces brain oedema and ICAM-1 expression at 24 h post-TBI. Rats given fenofibrate at 1, 6, 24, 48 and 72 It after TBI show neurological recovery associated with a reduction of the brain lesion at 7 days post-TBI. The present data represents the first demonstration that fenofibrate, a PPAR alpha agonist, exerts neuroprotective effects in TBI. The activation of receptor PPAR alpha could be beneficial by counteracting the deleterious inflammatory response following TBI. This suggests that PPAR alpha activation could be a new and promising therapeutic strategy for the treatment of brain trauma. (C) 2005 Elsevier Ireland Ltd. All rights reserved.