02 May 2003 : Original article
3-aminobenzamide, a poly(ADP-ribose)- polymerase inhibitor, reduces brain infarction and polymorphonuclear neutrophil infiltration after cerebral ischemia/reperfusion in mice
J. Couturier, N. Croci, M. Plotkine, I. MargaillMed Sci Monit 2003; 9(1): 16-0 :: ID: 15063
Abstract
Background:Poly(ADP-ribose) polymerase (PARP) was shown to be detrimental in cerebral ischemia but the mechanisms whereby PARP is deleterious have yet to be determined. They may include a role in polymorphonuclear neutrophil (PMN) infiltration known to aggravate ischemic damage. In this context, we investigated the effect of 3-aminobenzamide (3-AB), a PARP inhibitor, on brain damage and PMN infiltration in transient focal cerebral ischemia in mice.Material/Methods: Ischemia was induced in male Swiss mice, anaesthetized with chloral hydrate (400 mg/kg, i.p), by a 15 min-occlusion of the left middle cerebral artery using an intraluminal suture. Infarct volume was assessed 24 and 48 h after ischemia, and myeloperoxidase (MPO) activity used as an index of PMN infiltration at 48 h. Results:Treatment with 3-AB at 20, 40, 80 mg/kg, given i.p. 15 min before reperfusion, significantly reduced by 17–31% the infarct volume at 24 h. By contrast, 3-AB was devoid of neuroprotective activity at higher doses (160 and 320 mg/kg) or when treatment (40 mg/kg) was delayed by 2 h or 6 h after reperfusion. The neuroprotective effect of 3-AB (40 mg/kg, 15 min before reperfusion), was sustained up to 48 h after ischemia. With the same protocol, 3-AB also markedly reduced the PMN infiltration as evidenced by a 72%-decrease in MPO activity of damaged tissue at 48 h.Conclusions: Our results confirm that PARP activation contributes to brain damage. Moreover, for the first time, a quantitative study suggests that PARP is involved in PMN infiltration elicited by cerebral ischemia.
Keywords: poly(ADP-ribose) polymerase, cerebral ischemia, neutrophil, 3-aminobenzamide
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