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

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Abstract
THE activation of poly(ADP-ribose) polymerase (PARP) by free radical-damaged DNA plays a pivotal role in mediating ischemia-reperfusion injury. The purpose of the present study was to examine the neuroprotective effects of a PARP inhibitor, 3-aminobenzamide (3-ABA), which was administered either prior to or following reperfusion, to determine the importance of PARP inhibition prior to reperfusion. 3-ABA was injected i.p. either 15 min before or 15 min following reperfusion in a transient focal ischemia model in the rat. Treatment prior to the reperfusion led to a significant decrease in the volume of damaged tissue at 24 h (118.7 ± 18.8 mm3, mean ± s.d., p < 0.01), compared with the control (176.1 ± 22.8 mm3). However, treatment after the reperfusion failed to produce a reduction in the damaged volume (171.9 ± 27.6 mm3). These findings suggest that PARP activation sufficient to produce cellular damage occurs immediately after the reperfusion following cerebral ischemia.