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拉科酰胺对小鼠皮层扩展性去极化的影响。

Effect of lacosamide on cortical spreading depolarization in mice.

作者信息

Iba Chisato, Unekawa Miyuki, Ihara Keiko, Izawa Yoshikane, Nakahara Jin, Takizawa Tsubasa

机构信息

Department of Neurology, Keio University School of Medicine, Tokyo, 160-8582, Japan.

出版信息

J Headache Pain. 2025 Jul 16;26(1):163. doi: 10.1186/s10194-025-02099-9.

Abstract

BACKGROUND

Antiseizure medications are often used as preventive treatment of migraine in appropriate cases; however, the efficacy of lacosamide (LCM), a sodium channel blocker, in preventing migraine attacks remains unclear. Cortical spreading depolarization (CSD) refers to a wave of slowly propagating depolarization across the cerebral cortex. CSD animal models have been extensively used to investigate migraine attacks and evaluate the effects of migraine medication. Herein, we examined the effects of single dose LCM (40 mg/kg) on CSD sensitivity in a mouse model.

FINDINGS

Thirty-two C57BL/6 mice (male, n = 16; female, n = 16) were intraperitoneally injected with either LCM (40 mg/kg) or saline before CSD sensitivity testing. Potassium chloride (KCl) was administered to induce CSD, and the CSD threshold, frequency, and propagation velocity were determined. The average CSD frequency induced by 1 M KCl was significantly lower (p = 0.030) and the CSD propagation velocity tended to be lower in the female LCM group than in the saline group. However, no significant differences were observed in any of the three CSD parameters in male mice.

CONCLUSIONS

In female mice, single dose LCM treatment significantly reduced CSD frequency induced by KCl. Further investigations are warranted to assess the clinical potential of LCM in preventing migraine.

摘要

背景

在适当情况下,抗癫痫药物常被用作偏头痛的预防性治疗;然而,钠通道阻滞剂拉考沙胺(LCM)预防偏头痛发作的疗效仍不明确。皮层扩散性抑制(CSD)是指一波缓慢传播的去极化波穿过大脑皮层。CSD动物模型已被广泛用于研究偏头痛发作并评估偏头痛药物的效果。在此,我们在小鼠模型中研究了单剂量LCM(40mg/kg)对CSD敏感性的影响。

研究结果

32只C57BL/6小鼠(雄性,n = 16;雌性,n = 16)在进行CSD敏感性测试前,腹腔注射LCM(40mg/kg)或生理盐水。给予氯化钾(KCl)以诱导CSD,并测定CSD阈值、频率和传播速度。1M KCl诱导的平均CSD频率在雌性LCM组中显著低于生理盐水组(p = 0.030),且CSD传播速度在雌性LCM组中也趋于更低。然而,在雄性小鼠的三个CSD参数中均未观察到显著差异。

结论

在雌性小鼠中,单剂量LCM治疗显著降低了KCl诱导的CSD频率。有必要进一步研究以评估LCM预防偏头痛的临床潜力。

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