In our previous studies [5,8], dystrophin (an actin-binding protein [40]) immunoreactivity was detected in blood vessels and in astrocytic perivascular end-feet, and was down-regulated 12 hrs after SE prior to the appearance of vasogenic edema and down-regulation of SMI-71 immunoreactivity. With respect to this previous report, changes in SMI immunoreactivity would be causes/results of interaction between endothelial cells and perivascular astrocytes. In the present study, p65-Ser276, p65-Ser311, p65-Ser529, and p65-Ser536 phosphorylation was observed in astrocytes following SE. Furthermore, sTNFp55R infusion effectively inhibited p65-Ser276 and p65-Ser311phosphorylation in astrocytes following SE. Therefore, it is likely that enhanced p65-Ser276 and p65-Ser311 phosphorylation may be involved in TNF-α-mediated BBB disruption. However, sTNFp55R infusion could not prevent p65-Ser529 and p65-Ser536 phosphorylations from SE insults. Since p65-Ser529 and p65-Ser536 are phosphorylated by TNF-α and IL-1β [41], it is likely that IL-1β-mediated p65-Ser529/Ser536 phosphorylation may also play a role in SE-induced vasogenic edema. Therefore, our findings indicate that both TNF-α and IL-1β may be synergists to play either a direct (by endothelial cells) or indirect (by astrocytes) role in the maintenance of BBB permeability.