Sleep Science Laboratories, HAMRI Co. Ltd, Ibaraki, 306-0128, Japan.
Research Resources Division, RIKEN Center for Brain Science, Saitama, 351-0198, Japan.
Biochem Biophys Res Commun. 2020 May 7;525(3):595-599. doi: 10.1016/j.bbrc.2020.02.121. Epub 2020 Feb 27.
Treatment of epilepsy remains difficult because patients suffer from pharmacoresistant forms of the disease and drug side-effects. Thus, there is an urgent need to identify not only new antiepileptic drug candidates but also novel epileptic animal models. Here, we characterize seizures induced with kainic acid (KA) in the common marmoset (Callithrix jacchus). Adult marmosets received 0.1, 1, or 10 mg/kg of KA subcutaneously. All animals exhibited early convulsive behavior (seizure scores of I and II on the Racine scale). Seizure scores were low at lower KA doses, but the highest dose of KA tested triggered generalized seizures (scores IV and V on the Racine scale). We next performed preliminary evaluation of the efficacy of the antiepileptic drug diazepam. This drug at 1 mg/kg (delivered subcutaneously) prevented 10 mg/kg KA-induced stage V seizures. KA administration to marmosets reliably triggers generalized seizures; therefore, the marmoset is a useful animal model in which to analyze the seizures of a nonhuman primate brain and to develop new treatments for epilepsy.
治疗癫痫仍然具有挑战性，因为患者患有药物抗性形式的疾病和药物副作用。因此，不仅需要确定新的抗癫痫药物候选物，还需要确定新的癫痫动物模型。在这里，我们描述了用海人酸（KA）在普通狨猴（Callithrix jacchus）中诱导的癫痫发作。成年狨猴接受了 0.1、1 或 10 mg/kg 的 KA 皮下注射。所有动物均表现出早期惊厥行为（Racine 量表上的 I 和 II 级惊厥评分）。较低 KA 剂量下的惊厥评分较低，但测试的最高 KA 剂量引发全身性癫痫发作（Racine 量表上的 IV 和 V 级惊厥评分）。接下来，我们对抗癫痫药物地西泮的疗效进行了初步评估。该药物在 1 mg/kg（皮下给药）时可预防 10 mg/kg KA 诱导的 V 级癫痫发作。KA 给药至狨猴可可靠地引发全身性癫痫发作；因此，狨猴是一种有用的动物模型，可用于分析非人类灵长类动物大脑的癫痫发作，并开发新的癫痫治疗方法。
