Ameliorative Effects of GW1929, a Nonthiazolidinedione PPARγ Agonist,on Inflammation and Apoptosis in Focal Cerebral Ischemic-Reperfusion Injury

Abstract

PPARγ agonist; 2-(Benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine (GW1929) in focal cerebral ischemic-reperfusion (IR) injury in rats. Focal cerebral IR injury resulted significant brain infarction and neurological deficits in rats. A significant increase in various inflammatory mediators like COX-2, iNOS, MMP-9, TNFα and IL-6 and massive apoptotic DNA fragmentation was also observed in the IR challenged brains. GW1929 treatment significantly attenuated the neurological damage in focal cerebral IR injury. Neuroprotective effects of GW1929 were found to be associated with significant reduction in the COX-2, iNOS, MMP-9, TNFα and IL-6 levels. Together, we have also evaluated the effects of Pioglitazone, a clinically available thiazolidinedione PPARγ agonist, against focal cerebral IR injury. Like GW1929, Pioglitazone also showed beneficial effects in cerebral IR injury associated neurological damage but at the higher dose as compared to GW1929. Neuroprotective effects of PPARγ agonists were found to be associated with significant reduction in TUNEL positive cells in IR challenged brain. In summary, these results suggested the neuroprotective potential of PPARγ agonists in cerebral IR injury and these effects may be attributed to their anti-inflammatory and anti-apoptotic potential.