The Intrinsic PEDF is Regulated by PPARγ in Permanent Focal Cerebral Ischemia of Rat

Abstract

Inflammatory damage plays a pivotal role in cerebral ischemia and may represent a target for treatment. Pigment epithelium-derived factor (PEDF) is proven to possess neuroprotective property. But there is little known about the intrinsic PEDF after cerebral ischemia. This study evaluated the time course expression of the intrinsic PEDF and its underlying regulation mechanisms after cerebral ischemia. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion. Telmisartan (PPARγ agonist) and GW9662 (PPARγ antagonist) were systemically administered to explore the effect on PPARγ, PEDF, NF-κB and MMP-9 expression at 24 h after cerebral ischemia by western blot and qRT-PCR. The neurological deficits, brain water content and infarct volume were measured. Compared with normal group, the expressions of PEDF and PPARγ decreased, and the expression of NF-κB and MMP-9 increased at early stage after ischemia (P < 0.05). Compared with the vehicle group, the decrease of PEDF and PPARγ was significantly up-regulated and the increase of NF-κB and MMP-9 was down-regulated by telmisartan at 24 h (P < 0.05). The neurological deficits, brain water content and infarct volume were dramatically alleviated by telmisartan (P < 0.05). Telmisartan's effects were reversed by GW9662 co-administration (P < 0.05). The expression of intrinsic PEDF was down-regulated at the early stage of cerebral ischemia. The protective effects of intrinsic PEDF by activating PPARγ pathway may be one of the strategic targets for cerebral ischemic therapies.