Modulation of ATP level and PARP activity alters mode of neuronal cell death and shows anti-edema effect in the model of ischemic/reperfusion injury.

Abstract

Cellular energy status may be important in determining the mode of cell death induced by an oxidative stress and ischemic injury. Overactivation of nuclear enzyme poly(ADP-ribose) polymerase (PARP) causes dramatic ATP consumption and has an important role in necrotic cellular death mechanism. The present study was conducted to evaluate the effect of PARP inhibitor (3-AB) and NAD on ischemic cellular death mechanisms and ischemic volume in the rat MCA stroke model. Compared with non-treated group, the volume of infarction was decreased about 34% in 3-AB treated group, and 45% in 3-AB plus NAD treated group. Compared with non-treated group, in both groups, immunoreactivities of PAR and COX-2 were significantly reduced in ischemic regions. However, those of activated caspase-3 were significantly increased. These findings were more significant in 3-AB plus NAD group