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

Journal of Neuroinflammation

Tae-Cheon Kang¹  Soo Young Choi²  Hea Jin Ryu¹  Ji-Eun Kim³ 

[1] Institute of Epilepsy Research, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea;Department of Biomedical Sciences, College of Life Science, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea;Department of Neurology, UCSF, and Veterans Affairs Medical Center, San Francisco, California 94121, USA

关键词: Immunohistochemistry;    Epilepsy;    Endothelium;    Blood brain barrier;    Astrocyte;   

Others  :  1212891
DOI  :  10.1186/1742-2094-9-6

 received in 2011-08-08, accepted in 2012-01-12,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Kim et al; licensee BioMed Central Ltd.

【 图 表 】

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