Nicotinamide Reduces the Infarct Volume in a Rat Model of Transient Middle Cerebral Artery Occlusion.
- Author:
Min Sup LEE
1
;
Young Jun AHN
;
Ki Young CHOI
;
Gu KANG
;
Seong Sik KANG
;
Il Young CHEONG
;
Kun Jai LEE
;
Keun Woo KIM
Author Information
1. Department of Pathology, Kangwon National University College of Medicine, Chunchon, Korea. guk@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Nicotinamide;
PARP-1;
Nitrotyrosine;
Brain ischemia
- MeSH:
Adenosine Triphosphate;
Animals;
Brain;
Brain Injuries;
Brain Ischemia;
Immunohistochemistry;
Infarction;
Infarction, Middle Cerebral Artery*;
Middle Cerebral Artery*;
Models, Animal*;
Neurons;
Niacinamide*;
Polymers;
Rats*;
Rats, Sprague-Dawley;
Reperfusion;
Stroke
- From:Korean Journal of Pathology
2006;40(2):93-102
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Cerebral ischemia depletes ATP and causes irreversible tissue injury. Nicotinamide is a precursor of NAD+ and it is also a poly (ADP-ribose) polymerase (PARP) inhibitor that increases the neuronal ATP concentration and so protects against stroke. Therefore we examined whether nicotinamide could protect against cerebral ischemia by using a model of transient middle cerebral artery occlusion (MCAO) (reperfusion 2 h post ischemia) in Sprague-Dawley rats. METHODS: Nicotinamide (500 mg/kg) or normal saline was administered intraperitoneally 24 and 0 h before and after MCAO, respectively. The infarction volumes were determined with triphenyltetrazolium chloride staining 24 h after reperfusion. The nitrotyrosine, PAR polymer and PARP-1 expressions were examined by immunohistochemistry with using brain slices obtained from the rats that were sacrificed at 0, 15, 30, 60 and 120 min after reperfusion. RESULTS: The infarction volumes were significantly attenuated (21.8%, p<0.05). The nitrotyrosine expressions were increased at 0, 15 and 30 min, and those expressions for PARP polymer and PARP-1 were increased at 60 and 120 min, respectively. Nicotinamide partly reduced the expressions for nitrotyrosine and PAR polymer except for PARP-1. CONCLUSIONS: These results suggest that nicotinamide may attenuate ischemic brain injury through its antioxidant activity and the inhibition of PARP-1.
