PARP inhibitor PJ34 ameliorates cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory effects in a rat model

Abstract

Cerebral ischemia is a major health threat to humankind around the world, and the reperfusion methods may provoke irreversible damages to brain tissues, causing impairment of neurological function. The goal of this study is to investigate the potential neurological protective effect of PJ34, a well-characterized poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor, on cerebral ischemia–reperfusion (I/R)-induced injury of the rat model. The cerebral I/R rats were received (3, 6, or 12 mg/kg) injections of PJ34 or saline at 24 h, 6 h before middle cerebral artery occlusion (MCAO) and 1 h, 24 h, and 48 h after MCAO. All rats were subject to the neurological behavior tests by open field test and Morris water maze test. The expression of pro-inflammatory cytokines, Cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in cerebral tissues was also determined. Our results demonstrated that the administration of PJ34 dose-dependently ameliorated cerebral I/R-induced injury and improved neurological performance of cerebral I/R rats. We also revealed that PJ34 treatment effectively reduced COX2, iNOS, and pro-inflammatory cytokine levels in the I/R-induced injury tissues. Our finding further supports that inhibition of PARP-1 activity is beneficial for reducing post-I/R-induced brain damage via targeting inflammatory response.