Neurophamacological basic research for intractable epilepsy in childhood

儿童顽固性癫痫主要有大田原综合征、西氏综合征和Lennox-Gastant综合征。这些被归类为广泛性癫痫，并表现出年龄依赖性，因为疾病的发病是年龄特异性的。在项目的第一年，我们澄清了21日龄和30日龄小鼠对电休克全身性惊厥的明显癫痫易感性，但在42日龄小鼠中没有。茶碱治疗剂量仅在21日龄小鼠中诱导癫痫易感性。这一发现证实了临床证据，即茶碱的治疗剂量有时会引起学龄前儿童癫痫发作。作为一种癫痫模型，通常通过对杏仁核等的电刺激来进行点火。这是局部癫痫的模型。在项目的第二年，我们通过腹腔注射戊四唑（pentilentetrazole， PIZ）进行点火模型，作为全面性癫痫的模型。雄性小鼠（体重25-30g）每日分别腹腔注射PTZ 50mg/kg和40mg/kg。50mg/kg剂量组小鼠在实验后5 ~ 6天、8天出现阶段，但大部分小鼠因惊厥死亡。给药剂量为40mg/kg时，小鼠在实验后约20天出现第五阶段，但无一死亡。在此基础上，进一步评价组胺能神经元系统和常规抗癫痫药物对该癫痫模型的影响。

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.