Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via th
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ORIGINAL PAPER
Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol‑Induced Epilepsy via the COX‑2/NLRP3/ IL‑18 Pathway Rui Liu1 · Shuhua Wu2 · Chong Guo1 · Zhongbo Hu1 · Jiangtao Peng1 · Ke Guo1 · Xinfan Zhang1 · Jianmin Li1 Received: 3 March 2020 / Revised: 29 June 2020 / Accepted: 1 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Epilepsy · Ibuprofen · Cyclooxygenase-2 · NOD-like receptor 3 · Action potential · Neuroprotection
Introduction Epilepsy is among the most common and most complex of all neurological diseases, affecting over 70 million people worldwide. The vast majority of patients with epilepsy show long-term repetitive seizures that result in cognitive and behavioral disorders. The patients suffering from epilepsy usually requires lifelong medication therapy. However, approximately 30% of them do not respond to antiepileptic drugs. Therefore, a better understanding of the pathogenesis of epilepsy and novel more effective treatments are urgently needed. Accumulating evidence suggests that inflammatory Rui Liu and Shuhua Wu have contributed equally. * Jianmin Li [email protected] 1
Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China
Department of Pathology, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China
2
processes in the brain play a key role in this disease [1, 2]. Thus, anti-inflammatory therapies could have potential for the prevention and treatment of epilepsy. The inflammasome is a multi-protein complex that was
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