Neurophamacological basic research for intractable epilepsy in childhood

儿童时期的主要顽固性癫痫被称为大田原综合征、韦斯特综合征和Lennox-Gastant综合征。这些疾病被归类为全身性癫痫，并表现出年龄依赖性，因为疾病的发病是特定于年龄的。在项目的第一年，我们澄清了明显的癫痫发作易感性在21天大的小鼠和30天大的小鼠对电击全身性惊厥的易感性，但在42天大的小鼠中没有。治疗剂量的茶碱仅在21日龄小鼠中诱发癫痫易感性。这一发现证实了临床证据，治疗剂量的茶碱有时会导致学龄前儿童癫痫发作。点燃作为癫痫模型通常是通过电刺激杏仁核等部位进行的。这是一个部分性癫痫模型。在项目的第二年，我们通过腹腔注射戊四氮(PIZ)进行点燃模型作为全身性癫痫的模型。雄性小鼠(体重25~30g)，每天腹腔注射PTZ 50 mg/kg和40 mg/kg。当剂量为50 mg/kg时，小鼠在实验后8天出现5-6期，但大多数小鼠死于萎缩性胃病。当剂量为40 mg/kg时，小鼠在实验后20天左右进入第五阶段，但无一死亡。组胺能神经元系统和常规抗癫痫药物对该癫痫模型的作用将在未来进行评估。

Main intractable epilepsies in childhood are known as Ohtahara syndrome, West syndrome and Lennox-Gastant syndrome. These are categorized as generalized epilepsy and show age dependency as the onset of the disease is age specific.In the first year of the project, we clarified that obvions seizure susceptibility was demonstrated in 21 -day-old, and 30-day-old mice to electroshock generalized convulsion but not in 42-day-old mice. The therapeutic dose of theopliyline induced seizure susceptilility only in 21-day-old mice. This finding confirms the clinical evidence that the therapeutic dose of the ophylline sometimes induced seizures in preschool age children.Kindling as an epilepsy model is performed usually by electric stimulation in amygdala, etc. This is a model for partial epilepsey.In the second year of the project, we carried out kindling model by intraperitoneal injection of pentilentetrazole(PIZ) as a model of generalized epilepsy. For male mice (body weight : 25-30g), 50mg/kg and 40mg/kg of PTZ was intraperitoneally injected daily. By the dose of 50mg/kg, the mice showed stage 5-6, 8 days after the experiment but most of the mice died from comvulsion. By the dose of 40mg/kg, the mice showed stage 5 about20 days after the experiment, but none of the mice died. Then the effects of histaminergic neuron system and conventional antiepileptic agents will be evaluated to this epilepsy model in future.