Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, exerts neuroprotective effects in traumatic brain injury.
Peroxisome proliferator-activated receptor alpha (PPARalpha) 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 PPARalpha agonist, on the post-traumatic consequences caused by lateral fluid percussion of brain in rats. The effects of fenofibrate (50 and 100mg/kg) were evaluated on the consequences of TBI in the early phase (6 and 24h) 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 24h. Furthermore, fenofibrate reduces brain oedema and ICAM-1 expression at 24h post-TBI. Rats given fenofibrate at 1, 6, 24, 48 and 72h 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 PPARalpha agonist, exerts neuroprotective effects in TBI. The activation of receptor PPARalpha could be beneficial by counteracting the deleterious inflammatory response following TBI. This suggests that PPARalpha activation could be a new and promising therapeutic strategy for the treatment of brain trauma.
Besson
Valérie C
VC
Université Paris Descartes, Faculté de Pharmacie, Laboratoire de Pharmacologie de la Circulation Cérébrale, UPRES EA 2510, 4 avenue de l'Observatoire, F-75006 Paris, France.
Chen
Xiao R
XR
Plotkine
Michel
M
Marchand-Verrecchia
Catherine
C
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D000960:Hypolipidemic Agents; D018696:Neuroprotective Agents; D047493:PPAR alpha; D018799:Intercellular Adhesion Molecule-1; D011345:Fenofibrate