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Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway

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Abstract

Epilepsy is one of the most common diseases of the central nervous system. Recent studies have shown that a variety of inflammatory mediators play a key role in the pathogenesis of the disease. Ibuprofen (IBP) is a well-known anti-inflammatory agent that reduces the neuroinflammatory response and neuronal damage. In this study, we examined the effect of IBP in a rat model of pentylenetetrazol (PTZ)-induced chronic epilepsy. PTZ injection was given a total of 15 times on alternate days (over a period of 29 days) to induce epilepsy. The effects of IBP were evaluated by behavioral observation, EEG recording, Nissl staining, immunohistochemistry, Western blot analysis, and electrophysiological recording. The results showed that IBP alone affected the expression of cyclooxygenase-2 (COX-2) and neuronal excitability but did not cause epilepsy. IBP reduced seizure scores in the PTZ-treated rats, and it minimized the loss of hippocampal neurons. In addition, IBP decreased the secretion of COX-2, inhibited the activation of the NOD-like receptor 3 inflammasome, and reduced the secretion of the inflammatory cytokine interleukin-18. Furthermore, the results of whole-cell patch-clamp revealed that IBP affected action potential properties, including frequency, latency and duration in epileptic rats, suggesting that it may impact neuronal excitability. These effects of IBP may underlie its antiepileptic and neuroprotective actions.

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Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (to Shuhua Wu, No. 81772637), Shandong Medical and Health Technology Development Plan (to Zhongbo Hu, No. 2017WS553), Binzhou Medical University Science and Technology Plan Project (to Chong Guo, No. BY2015KJ13).

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  1. Rui Liu and Shuhua Wu have contributed equally.

Authors and Affiliations

  1. Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, 256603, Shandong, China

    Rui Liu, Chong Guo, Zhongbo Hu, Jiangtao Peng, Ke Guo, **nfan Zhang & Jianmin Li

  2. Department of Pathology, Binzhou Medical University Hospital, Binzhou, 256603, Shandong, China

    Shuhua Wu

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  1. Rui Liu
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Correspondence to Jianmin Li.

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All protocols were approved by the Institutional Animal Ethical Committee of Binzhou Medical University Hospital (China), and experiments were performed in accordance to the CPCSEA guidelines for ethical use of animals.

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Liu, R., Wu, S., Guo, C. et al. Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway. Neurochem Res 45, 2516–2526 (2020). https://doi.org/10.1007/s11064-020-03109-9

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