AUTHOR=Wu Chunfeng , Zhang Gang , Chen Lei , Kim Samuel , Yu Jie , Hu Guo , Chen Jing , Huang Yanjun , Zheng Guo , Huang Songming 

TITLE=The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury

JOURNAL=Frontiers in Neurology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01418

DOI=10.3389/fneur.2019.01418

ISSN=1664-2295

ABSTRACT=<p><bold>Objective:</bold> The objective of this study was to investigate the roles and mechanisms of inflammatory mediators NLRP3 and IL-1β in refractory temporal epilepsy brain injury.</p><p><bold>Method:</bold> First, the brain tissue and the peripheral blood of children undergoing intractable temporal lobe epilepsy surgery were analyzed as research objects. The expression levels of NLRP3 in brain tissue and IL-1β in blood were measured. A model of temporal lobe epilepsy was established using wild-type and NLRP3 knockout 129 mice. Pilocarpine was injected intraperitoneally into the experimental group, and isovolumetric saline was injected intraperitoneally into the control group (<italic>n</italic> = 8 in each group). The expression of IL-1β in the peripheral blood, cerebral cortex, and hippocampus of mice was measured by ELISA at 3 h, 24 h, 3 days, and 7 days after modeling. Fluoro-Jade B (FJB) and TUNEL methods were used to determine necrosis and apoptosis in hippocampal neurons, respectively, and the expression of NLRP3 in the cortex was measured by immunofluorescence methods.</p><p><bold>Result:</bold> (1) The IL-1β levels in the peripheral blood of children with intractable temporal lobe epilepsy were higher than those in the control group (<italic>t</italic> = 2.813, <italic>P</italic> = 0.01). There was also a positive correlation between IL-1β expression levels and the onset time of a single convulsion in patients with refractory epilepsy (<italic>r</italic> = 0.9735, <italic>P</italic> &lt; 0.05). The expression level of NLRP3 in the cerebral cortex of patients with refractory temporal lobe epilepsy was higher than that in the control group. (2) The expression level of NLRP3 in the hippocampus of wild-type mice increased 3 days after modeling and decreased slightly at 7 days but remained higher than that of the control group. IL-1β levels in peripheral blood were significantly higher than those in the control group at 3 days (<italic>t</italic> = 8.259, <italic>P</italic> &lt; 0.0001). The IL-1β levels in the peripheral blood of NLRP3 knockout mice were lower than those in the wild-type group at 3 days (<italic>t</italic> = 3.481, <italic>P</italic> = 0.004). At day 7, the neuronal necrosis and apoptosis levels in the CA3 region of the hippocampus decreased.</p><p><bold>Conclusion:</bold> NLRP3 may be involved in the development of refractory temporal lobe epilepsy. Inhibiting NLRP3 may alleviate local brain injury by downregulating the IL-1β expression. The IL-1β levels in the peripheral blood of patients with refractory temporal lobe epilepsy may reflect the severity of convulsions.</p>