BACKGROUND A hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model. METHODS The expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining. RESULTS The western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1β, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE. CONCLUSIONS Taken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects.

中文翻译：

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Rev-Erbα在颞叶癫痫癫痫灶中的表达降低和Rev-Erbα的激活在毛果芸香碱模型中具有抗炎和神经保护作用。

背景技术颞叶癫痫（TLE）的标志是伴随神经元死亡的脑炎症。越来越多的证据表明，Rev-Erbα参与调节神经炎症和决定神经元的命运。因此，我们在毛果芸香碱模型中研究了Rev-Erbα在TLE致痫区的表达和细胞分布，以及Rev-Erbα特异性激动剂SR9009的治疗效果。方法采用Western blotting，免疫组化和免疫荧光标记技术研究TLE患者中Rev-Erbα的表达模式。接下来，通过蛋白质印迹，免疫荧光标记染色和TUNEL染色评估SR9009对癫痫持续状态（SE）7天后小鼠海马神经炎症，神经元凋亡和神经元丢失的影响。结果Western印迹，免疫组织化学和免疫荧光标记结果表明，Rev-Erbα在TLE患者的癫痫发生区被下调，并且主要定位在神经元，星形胶质细胞和小胶质细胞中。同时，在深部SE后和慢性期，用毛果芸香碱处理的小鼠海马和颞新皮层中Rev-Erbα的表达降低。有趣的是，Rev-Erbα在正常海马中的表达表现出24小时的节律。然而，在SE后的早期，节律性受到了干扰，这种癫痫动物中仍然存在这种紊乱。我们的进一步发现表明，用SR9009进行治疗可抑制NLRP3炎性小体激活，炎性细胞因子（IL-1β，IL-18，IL-6和TNF-α）的产生，星形细胞增多症，小胶质细胞增生，SE后海马神经元的损伤 结论综上所述，这些结果表明在癫痫发生区中Rev-Erbα的减少可能有助于TLE的过程，并且Rev-Erbα的活化可能具有抗炎和神经保护作用。