Expression and correlation of the NOD-like receptor family, pyrin domain-containing 3 inflammasome and the silent information regulator 1 in patients with drug-resistant epilepsy

Abstract

Background

The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammatory pathway is implicated in the development of epilepsy and can be suppressed by the activation of the silent information regulator 1 (SIRT1). However, the expression and correlation of the NLRP3 pathway and SIRT1 in drug-resistant epilepsy (DRE) remain unknown.

Methods

This study evaluated the histopathology of the cerebral cortex from nine patients with DRE and eight patients with cavernous haemangioma undergoing surgical treatment. It analysed the expression of the NLRP3, interleukin-1β (IL-1β), caspase-1 and SIRT1 using immunohistochemistry. Additionally, the contents of NLRP3, caspase-1, IL-1β and SIRT1 in the serum samples of the included study participants were determined using ELISA method. The correlation between the NLRP3 pathway and the SIRT1 was assessed using Spearman’s correlation analysis.

Results

The expression of NLRP3, caspase-1 and IL-1β in the cerebral cortex of patients with DRE was elevated, with the NLRP3 expression being negatively correlated with the SIRT1 expression. Furthermore, IL-1β in serum was upregulated in patients with DRE. The correlation between the content of serum SIRT1 and NLRP3, caspase-1 and IL-1β in patients with DRE was not significant. Notably, serum caspase-1 levels were obviously higher in patients with bilateral hippocampal sclerosis than in patients with unilateral hippocampal sclerosis.

Conclusions

The current results indicate that the expression of the NLRP3/caspase-1/IL-1β pathway is significantly upregulated in patients with DRE and that it is partially correlated with the SIRT1 expression. This study is important for understanding the pathophysiology of DRE and developing new treatment strategies for it.