Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, 256603, Shandong, China.
Department of Pathology, Binzhou Medical University Hospital, Binzhou, 256603, Shandong, China.
Neurochem Res. 2020 Oct;45(10):2516-2526. doi: 10.1007/s11064-020-03109-9. Epub 2020 Aug 13.
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.
癫痫是中枢神经系统最常见的疾病之一。最近的研究表明，多种炎症介质在疾病的发病机制中起着关键作用。布洛芬（IBP）是一种众所周知的抗炎药，可减轻神经炎症反应和神经元损伤。在这项研究中，我们在戊四氮（PTZ）诱导的慢性癫痫大鼠模型中研究了 IBP 的作用。PTZ 总共在 29 天的时间内每隔一天注射 15 次（共 15 次）以诱导癫痫。通过行为观察、脑电图记录、尼氏染色、免疫组织化学、Western blot 分析和电生理记录评估 IBP 的作用。结果表明，IBP 单独影响环氧化酶-2（COX-2）和神经元兴奋性的表达，但不会引起癫痫。IBP 降低了 PTZ 处理大鼠的癫痫发作评分，并最大程度地减少了海马神经元的丢失。此外，IBP 降低了 COX-2 的分泌，抑制了 NOD 样受体 3 炎性小体的激活，并减少了炎性细胞因子白细胞介素-18 的分泌。此外，全细胞膜片钳记录的结果表明，IBP 影响了癫痫大鼠动作电位的特性，包括频率、潜伏期和持续时间，提示其可能影响神经元兴奋性。IBP 的这些作用可能是其抗癫痫和神经保护作用的基础。
