The effect of reperfusion on neuroprotection using an inhibitor of poly(ADP-ribose) polymerase

THE activation of poly(ADP-ribose) polymerase (PARP) by free radical-damage d DNA plays a pivotal role in mediating ischemia-reperfusion injury. The pu rpose of the present study was to examine the neuroprotective effects of a PARP inhibitor, 3-aminobenzamide (3-ABA), which was administered either pri or to or following reperfusion, to determine the importance of PARP inhibit ion prior to reperfusion. 3-ABA was injected i.p. either 15 min before or 1 5 min following reperfusion in a transient focal ischemia model in the rat. Treatment prior to the reperfusion led to a significant decrease in the vo lume of damaged tissue at 24 h (118.7 +/- 18.8 mm(3), mean +/- s.d., p < 0. 01), compared with the control (176.1 +/- 22.8 mm(3)). However, treatment a fter the reperfusion failed to produce a reduction in the damaged volume (1 71.9 +/- 27.6 mm(3)). These findings suggest that PARP activation sufficien t to produce cellular damage occurs immediately after the reperfusion follo wing cerebral ischemia. NeuroReport 10:2017-2022 (C) 1999 Lippincott Willia ms & Wilkins.