title: The effect of reperfusion on neuroprotection using an inhibitor of poly(ADP-ribose) polymerase.
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.
authors.affiliation: Cerebrovascular Research Center, University of Pennsylvania, Philadelphia 19104-6063, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: J H
authors.initials: JH
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury
chemical_list: D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors