Neurophamacological basic research for intractable epilepsy in childhood

儿童期难治性癫痫主要有大田原综合征、West综合征和Lennox-Gastant综合征。这些被归类为全身性癫痫，并显示出年龄依赖性，因为疾病的发作是年龄特异性的。在该项目的第一年，我们澄清了21日龄和30日龄小鼠对电击全身性惊厥的明显癫痫易感性，但在42日龄小鼠中没有。治疗剂量的茶碱仅在21日龄小鼠中诱导癫痫发作。这一发现证实了临床证据表明，治疗剂量的茶碱有时会诱发学龄前儿童癫痫发作。点燃作为癫痫模型，通常通过电刺激杏仁核等进行。这是一种部分性癫痫模型。在项目的第二年，我们通过腹腔注射戊替仑四唑（PIZ）进行点燃模型，作为全身性癫痫模型。对于雄性小鼠（体重：25- 30 g），每天腹腔注射50 mg/kg和40 mg/kg的PTZ。50 mg/kg剂量组小鼠在实验后第8天出现5-6期，但大部分小鼠死于惊厥。40 mg/kg剂量组小鼠在实验后20天左右出现5期，但无1只死亡。本研究将进一步探讨组胺能神经元系统及常规抗癫痫药物对该模型的影响。

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.