Abstract TP258: Oleic Acid Decreased Brain Infarct Volume In Middle Cerebral Artery Occlusion Rats By Peroxisome Proliferator-Activated Receptor γ Activation

Abstract

OA, a monounsaturated ω-9 fatty acid, is most abundant in all dietary fats and oils, especially olive oil, canola oil and high-oleic sunflower and safflower oil. OA was reported to have an anti-inflammatory effect by inhibiting reactive oxygen species (ROS), p38 MAPK, and Akt/IKK/NF-κB signaling pathways in LPS-stimulated BV2 microglia. The accumulation of FFAs after cerebral ischemia has been thought to contribute to injury-associated secondary brain damage by direct and indirect mechanisms. However, the role of OA has not been paid attention or known for exacerbating neuronal cell death in ischemic conditions. We hypothesized that OA may exert important role on the neuroprotective effect in ischemic rat brain and this effect exert through PPARγ activation. The infarct volume of systemic administration of OA in transient middle cerebral artery occlusion (MCAo) rat was measured after pretreatment of the PPARγ antagonist, GW9662 in order to determine whether PPARγ activation is critical for this effect, and the effect was compared with non-treated group. The expression of COX-2 and MMP-9 was investigated and the induction of HO-1 was also investigated by immunohistochemistry, RT-PCR and zymography in order to confirm the mechanism via activation of PPARγ. OA decreased infarct size induced by MCAo as late as 3 h after the injury, and the effect of OA was inhibited by the pretreatment of GW9662, a PPARγ antagonist. OA also inhibited the COX-2 and MMP-9 expression and induced HO-1 gene in MCAo rats. In conclusion, OA significantly reduces the infarct volume of MCAo rats through anti-inflammatory and anti-oxidative effect by acting, at least partly, as a PPARγ agonist. Given that this compound was administered as late as 3 h after the onset of the ischemic damage, OA might be very useful for stroke therapy.