Objective - Brain expresses abundant lipocalin-type prostaglandin (PG) D2 (PGD2) synthase but the role of PGD2 and its metabolite, 15-deoxy-Δ12,14 PGJ2 (15d-PGJ 2) 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-γ (PPARγ) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPARγ 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 PPARγ and HO-1 expression. The anti-apoptotic effect was abrogated by PPARγ inhibition. Conclusion - 15d-PGJ2 suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPARγ dependent manner. 15d-PGJ2 may play a role in controlling acute brain damage induced by ischemia-reperfusion.
|Number of pages||7|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Publication status||Published - Mar 2006|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine