Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood–brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.

中文翻译：

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Rufinamide (RUF) 在红藻氨酸诱导的脑损伤期间抑制炎症并维持血脑屏障的完整性

Rufinamide (RUF) 是一种结构独特的抗癫痫药物，但其对脑损伤的保护机制仍不清楚。在本研究中，我们验证了 RUF 如何保护具有红藻氨酸 (KA) 诱导的神经元损伤的小鼠。为此，通过KA腹腔注射建立小鼠癫痫模型。尼氏染色后，虽然用 KA、40、80 和 120 mg/kg 处理的小鼠的尼氏体显着减少，但 RUF 以剂量依赖性方式显着减少 KA 诱导的神经元损伤。其中，120 mg/kg RUF最为明显。免疫组织化学 (IHC) 和蛋白质印迹分析表明，RUF 抑制 KA 引起的 IBA-1 过表达，从而阻断小胶质细胞过度活化。此外，RUF 治疗部分逆转了神经炎性细胞因子（IL-1β、TNFα、HMGB1、和 NLRP3）在 KA 小鼠中 mRNA 和蛋白质水平的过表达。此外，虽然 KA 刺激抑制了紧密连接的表达，但 RUF 处理显着上调了 KA 小鼠脑组织中 mRNA 和蛋白质水平中紧密连接蛋白（occludin 和 claudin 5）的表达。RUF抑制小胶质细胞的过度活化，抑制神经炎症反应，减少血脑屏障的破坏，从而减轻KA小鼠的兴奋性神经损伤。