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31 October 2012

Using a novel in vivo model to study the function of nuclear factor kappa B in cerebral ischemic injury

Rui WangBCDE, Songlan LiangBFG, Hui YueFG, LIjie ChenABF

DOI: 10.12659/MSM.883539

Med Sci Monit 2012; 18(11): BR461-467

Abstract

Background: Cerebral ischemia is a situation with a deficit blood supply to the brain, which eventually leads to cell death, inflammation, and tissue damage. Nuclear factor kappa B (NF-kappaB) plays an important role in inflammation and immune regulation. The aim of this study was to test the function of the activation of NF-kappaB in vivo in cerebral ischemic injury.
Material/Methods: We generated an animal model that used the method of occlusion of the middle cerebral artery (MCAO). The 60 traits were equally divided into 5 groups to investigate the role of NAC pretreatment: (1) sham-operation (control), (2) ischemia for 6 hours, (3) ischemia for 6 hours and NAC pretreatment, (4) ischemia for 24 hours, (5) ischemia for 24 hours and NAC pretreatment. The 36 rats were divided randomly into 3 groups: (A) recombinant adenovirus expressing wild-type kappaBalpha (AdIkappaBalphaM) group, (B) recombinant adenovirus expressing wild-type IkappaBalpha (AdIkappaBalpha) group, and (C) simple ischemia group. Triphenyltetrazolium chloride (TTC) was used to measure infarct volume. Detection of expression of NF-kappaB was by Immunohistochemistry analysis.
Results: The infarct size of the 24-hours ischemia groups were bigger than those of 6-hours ischemia groups (P<0.01). The infarct size of using NAC pretreatment groups was obviously reduced compared with saline control groups (P<0.01).The percentage of cortical p65-positive cells of the group of (A) were significantly less than the groups of (B) and (C).
Conclusions: Our data suggest that N-acetylcysteine (NAC) and Ad-IkappaBalpha-Mut can inhibit the activation of NF-kappaB in vivo, reduce the focal infarct size, and protect the brain tissue in ischemia.

Keywords: Mutant Proteins - metabolism, I-kappa B Proteins - metabolism, Brain Ischemia - prevention & control, Acetylcysteine - therapeutic use, Rats, Wistar, Transcription Factor RelA - metabolism

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416