Abstract: OcjectiVe This study is to eXplore peroXisome proliferator-activated receptor gamma ( PPARγ)protecting rat brain against focal cerebral ischemic stroke and its mechanism. Methods Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion( MCAO ). Sprague-Dawley rats were randomly divided into four groups:sham-operated group,vehicle group,telmisartan group,and telmisartan+GW9662 group. At 24h after focal cerebral ischemia,the eXpression of PPARγ, pigment epithelium-derived factor(PEDF),matriX metalloproteinase-9(MMP-9)were eXplored by western blot and RT-PCR. The water content of brain tissue was measured by dry-wet weight method,the infarct volume was detected by TTC stain,and the nerve functions were evaluated with the improved Longva method. Results At 24h after MCAO PPARγ and PEDF eXpression significantly decreased,while MMP-9 increased in vehicle group. Telmisartan activating PPARγ dramatically up-regulated PEDF and down-regulated MMP-9,alleviated the neurological deficits,brain water content and infarct volume in telmisartan+GW9662 group,which were all abolished by GW9662 blocking PPARγas shown in telmisartan+GW9662 group. Conclusion PPARγ is the key factor in modulating the inflammatory reactions secondary to focal cerebral ischemia. PPARγ might be the potential therapeutic target for focal cerebral ischemia.

Key words: brain ischemia, peroXisome proliferator-activated receptors, matriX metalloproteinases 9