p65 phosphorylation of NF-κB enhances its transactivation potential, and p65 phosphorylation occurs in either the cytoplasm or the nucleus [30]. In the present study, p65-Thr435 immunoreactivity was detected in endothelial cells, and its immunoreactivity showed an inverse correlation to the degree of SMI-71 expression. SMI-71, an endothelial barrier antigen, is a protein expressed by endothelial cells of rat BBB [31]. Under pathological conditions, SMI-71 expression is lost in endothelial cells [5,7,8,30,32]. Acute phases of the above pathological conditions are accompanied by opening of the BBB and development of vasogenic edema [33]. Indeed, neutralization of SMI-71 in vivo leads to widening of intercellular junctions between endothelial cells and swelling of perivascular astrocytic processes [34], although SMI-71 is not localized at endothelial cell junctions [35-38]. In the present study, SMI-71 immunoreactivity was significantly reduced in blood vessels 1 day after SE when vasogenic edema and neuronal damage were observed. Furthermore, sTNFp55R infusion effectively prevented SE-induced SMI-71 down-regulation. With respect to the phosphorylation of p65-Thr435 by TNF-α [39], our findings indicate that TNF-α-mediated p65-Thr435 phosphorylation in endothelial cells may play an important role in vasogenic edema induction via SMI-71 degradation or its posttranslational dysfunction influencing BBB permeability.