3-Aminobenzamide reduces brain infarction and neutrophil infiltration after transient focal cerebral ischemia in mice.

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.

• 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)

Chemical References

• Benzamides
• Enzyme Inhibitors
• Neuroprotective Agents
• Poly(ADP-ribose) Polymerase Inhibitors
• 3-aminobenzamide
• Peroxidase

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