Why the study?
Does 3-aminobenzamide reduce the volume of damaged tissue in a rat model of transient focal ischemia?
Does 3-aminobenzamide reduce the volume of damaged tissue in a rat model of transient focal ischemia?
PARP inhibition with 3-ABA provides neuroprotection in transient focal ischemia only when administered prior to reperfusion, suggesting immediate PARP activation upon reperfusion.
Pre-reperfusion PARP inhibition attenuates rat infarct volume; hypothesis-generating for timed neuroprotection in clinical stroke.
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.
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Takahashi et al. (1999) studied this question.
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