All Title Author
Keywords Abstract

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

DOI: 10.1186/1742-2094-9-6

Keywords: Astrocyte, Blood brain barrier, Endothelium, Epilepsy, Immunohistochemistry

Full-Text   Cite this paper   Add to My Lib


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.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.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.Status epilepticus (SE) is a medical emergency with significant mortality [1]. SE has been defined as continuous seizure activity, which causes neuronal cell death, epileptogenesis and learning impairment [2,3]. Some brain regions vulnerable to SE play a role in the generation and propagation of paroxysmal activity in experimental epilepsy models. The piriform cortex (PC) is one of the most susceptible brain regions to seizure-induced damage in the kainate, pilocarpine and other models of temporal lobe epilepsy (TLE) [4-6]. Pilocarpine, a cholinergic agonist, induces SE in rodents. This pilocarpine-induced SE, similar to human TLE, shows massive neuronal loss in the hippocampus followed by glial proliferation. This neuronal damage in the pilocarpine model is not restricted to the hippocampus, but often extends to extrahippocampal limbic struc


comments powered by Disqus