The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury
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 an...
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doaj-9f9d09f372c54d4397d03311fc270d2b2020-11-24T21:03:02ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-02-011010.3389/fneur.2019.01418495168The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain InjuryChunfeng Wu0Gang Zhang1Lei Chen2Samuel Kim3Jie Yu4Guo Hu5Jing Chen6Yanjun Huang7Guo Zheng8Songming Huang9Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing, ChinaDepartment of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United StatesDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaObjective: 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.https://www.frontiersin.org/article/10.3389/fneur.2019.01418/fullrefractory temporal lobe epilepsyinflammatory factorNLRP3IL-1βbrain injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chunfeng Wu Gang Zhang Lei Chen Samuel Kim Jie Yu Guo Hu Jing Chen Yanjun Huang Guo Zheng Songming Huang |
spellingShingle |
Chunfeng Wu Gang Zhang Lei Chen Samuel Kim Jie Yu Guo Hu Jing Chen Yanjun Huang Guo Zheng Songming Huang The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury Frontiers in Neurology refractory temporal lobe epilepsy inflammatory factor NLRP3 IL-1β brain injury |
author_facet |
Chunfeng Wu Gang Zhang Lei Chen Samuel Kim Jie Yu Guo Hu Jing Chen Yanjun Huang Guo Zheng Songming Huang |
author_sort |
Chunfeng Wu |
title |
The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury |
title_short |
The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury |
title_full |
The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury |
title_fullStr |
The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury |
title_full_unstemmed |
The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury |
title_sort |
role of nlrp3 and il-1β in refractory epilepsy brain injury |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2020-02-01 |
description |
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. |
topic |
refractory temporal lobe epilepsy inflammatory factor NLRP3 IL-1β brain injury |
url |
https://www.frontiersin.org/article/10.3389/fneur.2019.01418/full |
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