The Role of NLRP3 and IL-1 beta in Refractory Epilepsy Brain Injury

• Type of Material: Article
• Authors: Chunfeng Wu, Nanjing Medical University; Gang Zhang, Emory University; Lei Chen, Nanjing Medical University; Samuel Kim, Emory University; Jie Yu, Nanjing Medical University; Guo Hu, Nanjing Medical University; Jing Chen, Emory University; Yanjun Huang, Nanjing Medical University; Guo Zheng, Nanjing Medical University; Songming Huang, Nanjing Medical University
• Language: English
• Date: 2020-02-07
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © Copyright © 2020 Wu, Zhang, Chen, Kim, Yu, Hu, Chen, Huang, Zheng and Huang.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fneur.2019.01418
• Title of Journal or Parent Work: FRONTIERS IN NEUROLOGY
• Volume: 10
• Start Page: 1418
• End Page: 1418
• Grant/Funding Information: This study was partly supported by the National Natural Science Foundation of China (81801292), Jiangsu Provincial Postdoctoral Science Foundation funded project (2019K257).
• Keywords: inflammatory factor; IL-1 beta; SEIZURES; INFLAMMATION; Science & Technology; Neurosciences & Neurology; NLRP3; Life Sciences & Biomedicine; MODEL; TEMPORAL-LOBE EPILEPSY; brain injury; refractory temporal lobe epilepsy; NECROSIS-FACTOR-ALPHA; Clinical Neurology; Neurosciences
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

Abstract

Objective: 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. Method: 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 (n = 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. Result: (1) The IL-1β levels in the peripheral blood of children with intractable temporal lobe epilepsy were higher than those in the control group (t = 2.813, P = 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 (r = 0.9735, P < 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 (t = 8.259, P < 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 (t = 3.481, P = 0.004). At day 7, the neuronal necrosis and apoptosis levels in the CA3 region of the hippocampus decreased. Conclusion: 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.