Korean J Pathol.  2006 Apr;40(2):93-102.

Nicotinamide Reduces the Infarct Volume in a Rat Model of Transient Middle Cerebral Artery Occlusion

• Lee MS
• Ahn YJ
• Choi KY
• Kang G
• Kang SS
• Cheong IY
• Lee KJ
• Kim KW

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.

Keyword

Nicotinamide; PARP-1; Nitrotyrosine; Brain ischemia

MeSH Terms

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
Adenosine Triphosphate
Niacinamide
Polymers