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

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-κB) plays an important role in inflammation and immune regulation. The aim of this study was to test the function of the activation of NF-κB in vivo in cerebral ischemic injury.

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 κBα(AdIκBαM) group, (B) recombinant adenovirus expressing wild-type IkappaBalpha (AdIκBα) group, and (C) simple ischemia group. Triphenyltetrazolium chloride (TTC) was used to measure infarct volume. Detection of expression of NF-κB was by Immunohistochemistry analysis.

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).

Our data suggest that N-acetylcysteine (NAC) and Ad-IκBα-Mut can inhibit the activation of NF-κB in vivo, reduce the focal infarct size, and protect the brain tissue in ischemia.