Effect of Poly (ADP-ribose) Polymerase Inhibitor Against the Ischemia/Reperfusion Injury in Ischemic Stroke Model.
- Author:
Seong Ho KOH
1
;
Seung Hyun KIM
;
Chi Won SONG
;
Hyugsung KWON
;
Yong Soon KIM
;
Sunjung KIM
;
Younjoo PARK
;
Ki Sok KIM
;
Hyun Jeung YU
;
Juhan KIM
;
Myung Ho KIM
;
Hai Kwan JUNG
Author Information
1. Department of Neurology, College of Medicine, Hanyang University, Korea.kimsh1@hanyang.ac.kr
- Publication Type:Original Article
- Keywords:
Stroke;
PARP;
Caspase-3;
PARP inhibitor
- MeSH:
Animals;
Apoptosis;
Caspase 3;
Cell Death;
DNA Damage;
DNA Repair;
Infarction;
Middle Cerebral Artery;
Rats;
Reperfusion;
Stroke*
- From:Journal of the Korean Neurological Association
2003;21(6):634-641
- CountryRepublic of Korea
- Language:Korean
-
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.