15d-prostaglandin J2 activates peroxisome proliferator-activated receptor-γ, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPAR gamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d- PGJ(2)) acts as a physiologic agonist for PPARc. In this study, we found that injection of 15d- PGJ(2) into the locus of striatal hematoma increased PPAR gamma-deoxyribonucleic acid ( DNA) binding activity and the expression of catalase messenger ribonucleic acid ( mRNA) and protein in the perihemorrhagic area. Additionally, 15d- PGJ(2) significantly reduced nuclear factor-kappa B (NF-kappa B) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d- PGJ(2) reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d- PGJ(2) at the onset of ICH is associated with activation of PPAR gamma and elevation of catalase expression, suppression of NF-kappa B activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.