Introduction
The neuroinflammatory response following traumatic brain injury (TBI) leads to the formation of edema, the production of cytokines, the induction of NOS2 and COX2, the parenchyma infiltration by leukocytes1, 2 and a deleterious oxidative stress 3 . As it has been demonstrated that inflammatory markers and antioxidant enzymes could be modulated by the activation of Peroxisome Proliferator-Activated Receptor α (PPARα) 4 , this led us to study the effect of fenofibrate, a PPARα agonist, on the consequences caused by TBI.
Materials
Male Sprague Dawley rats were randomised in five groups: non-operated (n=8), sham-operated (n=8), TBI + vehicle (n=8), TBI + fenofibrate 50 mg/kg (n=8) and TBI + fenofibrate 100 mg/kg (n=8). TBI was induced by lateral fluid percussion of the temporoparietal cortex 5 . Sham-operated rats underwent the same surgery except for percussion. Rats were given fenofibrate (50 and 100 mg/kg) or its vehicle (water containing 0.2% methylcellulose) by gavage 1 h and 6 h after TBI. A first neurological evaluation was performed 6 h post-TBI (score ranging from 0=worst to 9=best). The rats were then given the second administration of fenofibrate or its vehicle. The second neurological evaluation was performed at 24 h, then animals were killed for brain edema determination. Brain edema was obtained with the brain water content (BWC) measured by the wet weight/dry weight method 2 .
Results
Neurological scores of non-operated and sham-operated rats were not different. TBI led to a decrease in the neurological score at 6 h (6.0 ± 0.5 vs 8.6 ± 0.4 for sham-operated rats, P < 0.01) that persisted at 24 h post-injury (5.1 ± 0.7, P < 0.001). Six hours post-TBI, both doses of fenofibrate did not modify the neurological score (50 mg/kg: 6.4 ± 0.9; 100 mg/kg: 6.6 ± 0.7). Twenty-four hours post-injury, fenofibrate at 50 mg/kg improved the neurological score without reaching the statistical significance (7.1 ± 0.7, P=0.09). At 100 mg/kg, we observed a significant increase of the score demonstrating a neurological recovery (7.6 ± 0.5, P<0.05). The brain water contents of non-operated and sham-operated were not different. TBI led to an increase of the BWC (84.9 ± 0.5 % vs 80.6 ± 0.2 % for sham-operated rats, P<0.001) showing brain edema formation, which is reduced by the two doses of fenofibrate (82.7 ± 0.8 %, P < 0.05 and 83.3 ± 0.9 %, P < 0.05).
Conclusion
The present study shows that fenofibrate, a PPARα agonist, promotes neurological recovery and exerts anti-edematous effect in the early phase after TBI. The activation of receptor PPARα may be beneficial by counteracting the deleterious neuroinflammatory response following TBI. This suggests that PPARα activation could be a potential therapeutic strategy for TBI.