Indexed on: 14 Sep '16Published on: 14 Sep '16Published in: Neuroscience
Brain-blood barrier (BBB) disruption results in vasogenic edema, which is involved in the pathogenesis of epilepsy. Following status epilepticus (SE), up-regulated transient receptor potential canonical channel-3 (TRPC3), a Ca(2+)-permeable cation channels in endothelial cells, is relevant to vasogenic edema formation in the rat piriform cortex. In addition, pyrazole-3 (Pyr-3, a TRPC3 inhibitor) attenuated SE-induced vasogenic edema. However, the upstream regulators of TRPC3 expression in vasogenic edema formation have been unclear. In the present study, soluble tumor necrosis factor p55 receptor (sTNFp55R, a TNF-α inhibitor), SN50 (a nuclear factor-κB (NFκB) inhibitor), BQ-788 (an endothelin B (ETB) receptor inhibitor) and Pyr-3 effectively prevented vasogenic edema following SE. sTNFp55R and SN50 (but not BQ-788) attenuated SE-induced up-regulation of endothelial TRPC3 expression. Pyr-3 ameliorated SE-induced NFκB p65-Thr435 phosphorylation and ETB receptor expression. In addition, Pyr-3 mitigated NFκB p65-Thr435 phosphorylation induced by recombinant TNF-α. These findings indicate that TNF-α-mediated NFκB p65-Thr435 phosphorylation may up-regulate TRPC3 expression, which participates in vasogenic edema formation via increasing endothelial nitric oxide synthase expression following SE, independent of ETB receptor activation. Therefore, we suggest that TRPC3 may be involved in a positive feedback loop of NFκB/ETB receptor signaling pathway.
Indexed on: 14 Jan '12
Published on: 14 Jan '12 in Journal of neuroinflammation