Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea.
Arch Pharm Res. 2018 Jul;41(7):776-783. doi: 10.1007/s12272-018-1043-1. Epub 2018 Jun 8.
Rufinamide (RUF) is a structurally unique anti-epileptic drug, used in the treatment of seizure disorders such as Lennox-Gastaut syndrome. In the present study, we investigated whether RUF protected against excitotoxic neuronal damage in the mouse hippocampal CA3 region after intraperitoneal kainic acid (KA) injection. Treatment with 25, 50 and 100 mg/kg RUF significantly decreased the KA-induced neuronal death in the hippocampal CA3 region in a dose-dependent manner. In addition, 100 mg/kg RUF treatment reduced the KA-induced oxidative stress-related increase of MDA level and decrease of total SOD activity in the hippocampus. KA-induced increases of pro-inflammatory cytokines, TNF-α and IL-1β, levels as well as KA-induced microglial activation were also suppressed by RUF treatment. These results indicate that RUF displays a neuroprotective effect against KA-induced excitotoxic neuronal death in the mouse hippocampus through anti-oxidant and anti-inflammatory activities.
氨己烯酸（RUF）是一种结构独特的抗癫痫药物，用于治疗 Lennox-Gastaut 综合征等癫痫发作疾病。在本研究中，我们研究了腹腔注射海人酸（KA）后，RUF 是否对小鼠海马 CA3 区的兴奋性神经元损伤具有保护作用。RUF 以 25、50 和 100mg/kg 的剂量治疗可显著降低海马 CA3 区的 KA 诱导的神经元死亡，呈剂量依赖性。此外，100mg/kg RUF 治疗可降低海马中与氧化应激相关的 MDA 水平升高和总 SOD 活性降低。RUF 治疗还抑制了 KA 诱导的促炎细胞因子 TNF-α 和 IL-1β 水平的升高以及 KA 诱导的小胶质细胞激活。这些结果表明，RUF 通过抗氧化和抗炎活性对小鼠海马中 KA 诱导的兴奋性神经元死亡表现出神经保护作用。
