Neuroprotective effect of PARP inhibitor,3-Aminobenzamide on ischemic cell death by enhancing survival signal and inhibiting both inflammation and PARP activity

Abstract

Poly(ADP-ribose) polymerase (PARP) plays an important role in ischemic cell death, and 3-aminobenzamide (3-AB), one of PARP inhibitors, has a protective effect on ischemic stroke, but the exact mechanisms have not yet clearly delineated. Objectives: This study was designed to investigatie the effect 3-AB on morphological features and temporal sequential changes of biochemical markers including inflammatory, cell death and survival signals in ischemic region. Method : The occlusion of the left middle cerebral artery (MCA) was made in 170 Sprague-Dawley (SD) rats and reperfusion was done 2 hours after the occlusion. Other 10 SD rats were used for sham operation. 3-AB was administered to 85 rats 10 minutes before the occlusion [3-AB group (n=85) vs. control group without 3-AB (n=85)]. Infarct volume and water content were measured, brain MRI , TUNEL and cresyl violet staining were done, and immunoreactivities (IRs) of poly(ADP-ribose) polymer (PAR), cleaved caspase-3, CD11b, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), phospho-Akt (pAkt), and phospho-glycogen synthase kinase-3 (pGSK-3) were compared in the peri-infarcted region of the 3-AB group and its corresponding ischemic region of the control group at 2, 8, 24, and 72 hours after the occlusion