The major findings in the present study are that TNF-α signaling showed cellular specific responses of NF-κB phosphorylation in the PC following SE, which may be related to vasogenic edema formation followed by neutrophil infiltration. BBB disruption has been reported in experimental and human epilepsy [12,13,15,16,28]. Leakage of serum-derived components into the extracellular space is associated with hyperexcitability and seizure onset [12,13,15,16,28]. Furthermore, dysfunction of the BBB leads to epileptogenesis and contributes to progression of epilepsy [12,13,15,16,28]. In the present study, TNF-α immunoreactivity was obviously observed in microglia in the PC following SE. TNF receptor expressions were also up-regulated in astrocytes (TNFp55R and TNFp75R) and endothelial cells (TNFp75R). Furthermore, blockade of TNF-α signaling by sTNFp55 infusion effectively (but not completely) reduced volumes of SE-induced vasogenic edema and neuronal damage in the PC. These findings indicate that TNF-α may participate in astroglial and endothelial responses to SE, which are relevant to SE-induced vasogenic edema formation [5-8]. Indeed, TNF-α signaling increases BBB permeability in various experimental disease models [29]. In the present study, sTNFp55 infusion could not completely prevent SE-induced vasogenic edema and neuronal damage in the PC. Therefore, our findings suggest that TNF-α signaling may not be a unique upstream event in vasogenic edema development.