15d-prostaglandin J2 protects brain from ischemia-reperfusion injury.

OBJECTIVE Brain expresses abundant lipocalin-type prostaglandin (PG) D2 (PGD2) synthase but the role of PGD2 and its metabolite, 15-deoxy-Delta(12,14) PGJ2 (15d-PGJ2) in brain protection is unclear. The aim of this study is to assess the effect of 15d-PGJ2 on neuroprotection. METHODS AND RESULTS Adenoviral transfer of cyclooxygenase-1 (Adv-COX-1) was used to amplify the production of 15d-PGJ2 in ischemic cortex in a rat focal infarction model. Cortical 15d-PGJ2 in Adv-COX-1-treated rats was increased by 3-fold over control, which was correlated with reduced infarct volume and activated caspase 3, and increased peroxisome proliferator activated receptor-gamma (PPARgamma) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPARgamma inhibitor. Rosiglitazone infusion had a similar effect. 15d-PGJ2 and rosiglitazone at low concentrations suppressed H2O2-induced rat or human neuronal apoptosis and necrosis and induced PPARgamma and HO-1 expression. The anti-apoptotic effect was abrogated by PPARgamma inhibition. CONCLUSIONS 15d-PGJ2 suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPARgamma dependent manner. 15d-PGJ2 may play a role in controlling acute brain damage induced by ischemia-reperfusion.