Poly(ADP-ribose) polymerase inhibitors attenuate necrotic but not apoptotic neuronal death in experimental models of cerebral ischemia

摘要: An excessive activation of poly(ADP-ribose) polymerase (PARP) has been proposed to play a key role in post-ischemic neuronal death. We examined the neuroprotective effects PARP inhibitors benzamide, 6(5H)-phenanthridinone, and 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinone three rodent models cerebral ischemia. Increasing concentrations attenuated injury induced by 60 min oxygen-glucose deprivation (OGD) mixed cortical cell cultures, but were unable reduce CA1 pyramidal loss organotypic hippocampal slices exposed 30 OGD or gerbils following 5 bilateral carotid occlusion. then necrotic apoptotic features OGD-induced neurodegeneration cells using biochemical morphological approaches. Cortical released lactate dehydrogenase into medium displayed ultrastructural death, whereas no caspase-3 nor characteristics apoptosis observed at any time point after OGD. In contrast, marked increase activity was OGD, together with fluorescence electron microscope evidence death subregion. Moreover, caspase inhibitor Z-VAD-FMK reduced loss. These findings suggest that overactivation may be an important mechanism leading not type.