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

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) 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 PPARγ 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-Δ12,14-prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARγ. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARγ-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-κB (NF-κB) 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-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARγ and elevation of catalase expression, suppression of NF-κB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.