Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus

Background: status epilepticus (se) induces severe vasogenic edema in the piriform cortex (pc) accompanied by neuronal and astroglial damages. to elucidate the mechanism of se-induced vasogenic edema,we investigated the roles of tumor necrosis factor (tnf)-α in blood-brain barrier (bbb) disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced se.methods: se was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-,and soluble tnf p55 receptor (stnfp55r) prior to se induction. thereafter,we performed fluoro-jade b staining and immunohistochemical studies for tnf-α and nf-κb subunits.results: following se,most activated microglia showed strong tnf-α immunoreactivity. in addition,tnf p75 receptor expression was detected in endothelial cells as well as astrocytes. in addition,only p65-thr435 phosphorylation was increased in endothelial cells accompanied by smi-71 expression (an endothelial barrier antigen). neutralization of tnf-α by soluble tnf p55 receptor (stnfp55r) infusion attenuated se-induced vasogenic edema and neuronal damages via inhibition of p65-thr435 phosphorylation in endothelial cells. furthermore,stnfp55r infusion reduced se-induced neutrophil infiltration in the pc.conclusion: these findings suggest that impairments of endothelial cell functions via tnf-α-mediated p65-thr 485 nf-κb phosphorylation may be involved in se-induced vasogenic edema. subsequently,vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss. © 2012 kim et al; licensee biomed central ltd.