Abstract |
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 neutrophil 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 neutrophil infiltration after transient focal cerebral ischemia in mice. 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. Treatments with 3-AB were first administered intraperitoneally 15 min before reperfusion and endpoints measured at 24 h. Among the range of dosages studied (20-320 mg/kg), 40 mg/kg gave the maximal neuroprotection with a 30% decrease in the infarct volume and tended to improve the neurological score evaluated by a grip test. The same dosage was, however, devoid of effect when injection was delayed 2 or 6 h after reperfusion. Myeloperoxidase (MPO) activity used as an index of neutrophil infiltration showed that infiltration peaked 48 h after reperfusion in our model. At this time point, 3-AB (40 mg/kg given 15 min before reperfusion) markedly reduced the neutrophil infiltration, as evidenced by a 72%-decrease in MPO activity, and was still neuroprotective. Our results confirm that 3-AB reduces brain damage. Moreover, for the first time, a quantitative study shows that 3-AB decreases neutrophil infiltration elicited by cerebral ischemia.
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Authors | Jérôme Y Couturier, Li Ding-Zhou, Nicole Croci, Michel Plotkine, Isabelle Margaill |
Journal | Experimental neurology
(Exp Neurol)
Vol. 184
Issue 2
Pg. 973-80
(Dec 2003)
ISSN: 0014-4886 [Print] United States |
PMID | 14769390
(Publication Type: Journal Article)
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Chemical References |
- Benzamides
- Enzyme Inhibitors
- Neuroprotective Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- 3-aminobenzamide
- Peroxidase
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Topics |
- Animals
- Benzamides
(pharmacology)
- Brain Infarction
(drug therapy, etiology, pathology)
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- Ischemic Attack, Transient
(complications)
- Male
- Mice
- Neuroprotective Agents
(pharmacology)
- Neutrophil Infiltration
(drug effects)
- Peroxidase
(metabolism)
- Poly(ADP-ribose) Polymerase Inhibitors
- Reperfusion
- Time Factors
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