Neuronal expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and 15d-prostaglandin J2 -: Mediated protection of brain after experimental cerebral ischemia in rat

Existing experimental evidence suggests that PPAR gamma may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPAR gamma messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPAR gamma mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPAR gamma in neurons after ischemia. Intraventricular injection of 15d-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a proposed endogenous PPAR gamma agonist, into the ischemic rat brains significantly increased the PPAR gamma-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPAR gamma up-regulation in response to ischemia may contribute to PPAR gamma activation in the presence of PPAR gamma agonists. Activation of PPAR gamma in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury. (c) 2006 Elsevier B.V. All rights reserved.