Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus

Huang, Cheng; Chi, Xiao-sa; Li, Rui; Hu, Xin; Xu, Hai-xia; Li, Jin-mei; Zhou, Dong

doi:10.1007/s12031-017-0968-z

Published: 30 August 2017

Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus

Cheng Huang^1,2,
Xiao-sa Chi^2,3,
Rui Li⁴,
Xin Hu⁵,
Hai-xia Xu⁶,
Jin-mei Li² &
Dong Zhou ORCID: orcid.org/0000-0001-7101-4125²

Journal of Molecular Neuroscience volume 63, pages 173–184 (2017)Cite this article

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Abstract

P2X7 receptor (P2X7R) has been reported participating in neuroinflammation in multiple neurological diseases. We explored the role of P2X7R in a rat status epilepticus (SE) model induced by coriaria lactone (CL) and its association with neuroinflammation. Thirty minutes after intracerebroventricular infusion with P2X7R antagonists Brilliant blue G (BBG), A-438079, A-740003, or agonists 2′,3′-O-(4-benzoylbenzoyl)-adenosine 5′-triphosphate (BzATP), SE was induced by intramuscular injection of CL in Sprague-Dawley rats. Seizures severity was recorded according to the Racine scale and Morris water maze test was performed. P2X7R expression was measured by western blotting. Immunohistochemical staining was performed to assess pro-inflammation cytokines expression, neuronal loss, and astrocyte activation. The results showed P2X7R level began to increase at 1 day, peaked at 2 days, and gradually decreased to baseline by 2 weeks in rat hippocampus after SE. P2X7R activation induced NF-κB phosphorylation, along with increased IL-1β and IL-6 expression. Pretreatment with P2X7R antagonists ameliorated SE-induced neuroinflammation, neuronal damage, and astroglial and microglial activation to variable extent. In addition, these antagonists ameliorated seizure severity and improved cognitive function. These findings suggest P2X7R activation plays a critical role in epileptogenesis via regulation of neuroinflammation and blocking P2X7R may be a novel therapeutic strategy for epilepsy.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Item Number: 81501127).

Author information

Cheng Huang and Xiao-sa Chi contributed equally to this work.

Affiliations

Rehabilitation Medicine Center, West China Hospital of Sichuan University, Chengdu, 610041, China
Cheng Huang
Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China
Cheng Huang, Xiao-sa Chi, Jin-mei Li & Dong Zhou
Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266021, China
Xiao-sa Chi
Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital, Sichuan University, Chengdu, 610041, China
Rui Li
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China
Xin Hu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
Hai-xia Xu

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Cheng Huang
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Xiao-sa Chi
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Rui Li
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Xin Hu
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Hai-xia Xu
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Jin-mei Li
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Dong Zhou
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Contributions

D.Z. and J.-M.L. conceived and designed the experiments; C.H. and X.-S.C. performed the experiments and wrote the paper; and X.H. and H.-X.X. contributed materials and analysis tools and protocols.

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Correspondence to Dong Zhou.

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Huang, C., Chi, Xs., Li, R. et al. Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus. J Mol Neurosci 63, 173–184 (2017). https://doi.org/10.1007/s12031-017-0968-z

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Received: 03 June 2017
Accepted: 21 August 2017
Published: 30 August 2017
Issue Date: October 2017
DOI: https://doi.org/10.1007/s12031-017-0968-z

Keywords

P2X7 receptor
Neuroinflammation
Epilepsy
Hippocampus
Status epilepticus