Effect of Poly (ADP-ribose) Polymerase Inhibitor Against the Ischemia/Reperfusion Injury in Ischemic Stroke Model

J Korean Neurol Assoc > Volume 21(6); 2003 > Article

Journal of the Korean Neurological Association 2003;21(6): 634-641.

"허혈성 뇌졸중 모델에서 허혈 및 재관류 손상에 대한 Poly (ADP-ribose) Polymerase 억제제의 효과"

고성호 , 김승현 송치원 권혁성 김용순 김선정 박윤주 김기석 유현정

한양대학교 의과대학 신경과학교실*, 식품의약품안전청 국립독성연구원 일반독성부 신경독성과†, 분당제생병원 신경과학교실

Effect of Poly (ADP-ribose) Polymerase Inhibitor Against the Ischemia/Reperfusion Injury in Ischemic Stroke Model

Seong-Ho Koh

"Department of Neurology, College of Medicine, Hanyang University*, Division of Neurotoxicology, National Institute of Toxicological Research, KFDA†, Department of Neurology, Pundang Jesaeng Hospita"

Abstract

Background:Nuclear enzyme poly (ADP-ribose) polymerase (PARP) activated by DNA damage participates in DNA repair. However, overactivation of PARP could be an important pathogenic mechanism of ischemic cell death. We investigated the protective effect of an inhibitor of PARP, 3-aminobenzamide (3-AB), against ischemia/reperfusion injury in ischemic stroke model.
Methods:Occlusion of left middle cerebral artery (MCA) was done by intraluminal filament technique in 24 rats weighing from 315 g to 358 g, and reperfusion was done at 2 hours after occlusion. To evaluate the effect of PARP inhibitor in ischemic stroke, 3-AB was administered to 12 rats (3-AB group) 10 minutes before artificial occlusion of left MCA. Infarct area was confirmed by using 2,3,5-triphenyltetrazolium chloride stain. The immunoreactivities of poly (ADP-ribose) reflecting activity of enzyme PARP and activated caspase-3 were compared in infarct, peri-infarct and normal zones in 3-AB group and 12 controls.
Results:The volume of infarction was decreased about 34% in 3-AB group compared with controls. In 3-AB group, immunoreactivities of PAR were significantly reduced in ischemic regions, especially peri-infarct zone, but those of activated caspase-3 were significantly increased in same region.
Conclusions:These results suggest that treatment of PARP inhibitor can reduce the infarct volume by converting necrotic cell death into apoptosis. PARP inhibition can be another potential neuroprotective strategy in ischemic stroke.Key Words: Stroke, PARP, Caspase-3, PARP inhibitor