Department of Neurosurgery, School of Medicine, Oita University, Hasama-machi, Oita, Japan.
Neuroreport. 2023 Jan 14;34(1):61-66. doi: 10.1097/WNR.0000000000001859. Epub 2022 Nov 30.
The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice.
Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.c.)-induced SE (Pilo group) and lamotrigine (20 mg/kg, i.p.) treated (Pilo/lamotrigine group). The latency to SE of Racine's stage 3 or higher, the mortality rate within 2 h of Pilo administration, and the duration of SE until sacrifice were examined. Nitric oxide (NO), malondialdehyde and glutathione of oxidative stress biomarkers were detected in the hippocampus of the sacrificed animals in the above groups. NO was also detected in the cultured rat hippocampal neurons treated with 4 μM Pilo, Pilo+100 μM lamotrigine (Pilo/lamotrigine) and Pilo/lamotrigine+ N-methyl-D-aspartic acid (NMDA) receptor antagonist (10 μM MK-801, 3 μM ifenprodil) to examine the antioxidant effects of lamotrigine via non-NMDA-related pathways.
lamotrigine prolonged the latency to SE, the SE duration until sacrifice, and decreased the mortality rate in mice with Pilo-induced SE. Lamotrigine also decreased hippocampal concentrations of NO and malondialdehyde and increased the concentrations of glutathione in the SE model. Furthermore, there were significant differences in NO concentrations between groups of cultured rat hippocampal neurons treated with Pilo and Pilo/lamotrigine, and with Pilo/lamotrigine and Pilo/lamotrigine+MK-801.
Our findings suggest that lamotrigine exerts anticonvulsant and antioxidant effects on SE, but its antioxidant activity may not be fully exerted via NMDA-related pathways.
拉莫三嗪对癫痫持续状态（SE）的抗惊厥和抗氧化作用尚不完全清楚。我们评估了拉莫三嗪对匹罗卡品（Pilo）诱导的 SE 小鼠模型的影响。
雄性 C57BL/J6 小鼠被分为三组：对照组、匹罗卡品（400mg/kg，sc）诱导 SE（Pilo 组）和拉莫三嗪（20mg/kg，ip）治疗（Pilo/拉莫三嗪组）。观察 Racine 3 级或以上 SE 的潜伏期、匹罗卡品给药后 2 小时内的死亡率以及直至处死的 SE 持续时间。检测上述各组处死动物海马组织中的氧化应激生物标志物一氧化氮（NO）、丙二醛和谷胱甘肽。还检测了用 4μM 匹罗卡品、匹罗卡品+100μM 拉莫三嗪（Pilo/拉莫三嗪）和匹罗卡品/拉莫三嗪+N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（10μM MK-801、3μM ifenprodil）处理的培养大鼠海马神经元中的 NO，以检查拉莫三嗪通过非-NMDA 相关途径的抗氧化作用。
拉莫三嗪延长了匹罗卡品诱导 SE 的潜伏期、SE 持续时间直至处死，并降低了 SE 模型中小鼠的死亡率。拉莫三嗪还降低了 SE 模型中海马组织中 NO 和丙二醛的浓度，增加了谷胱甘肽的浓度。此外，用匹罗卡品和匹罗卡品/拉莫三嗪处理的培养大鼠海马神经元组之间以及用匹罗卡品/拉莫三嗪和匹罗卡品/拉莫三嗪+MK-801 处理的组之间的 NO 浓度存在显著差异。
我们的研究结果表明，拉莫三嗪对 SE 具有抗惊厥和抗氧化作用，但它的抗氧化活性可能不完全通过 NMDA 相关途径发挥作用。
