Development of a animal model of acute encephalopathy and an antibody therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670500
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Okayama University (2015-2016); Kyoto University (2014)
• Principal Investigator: Ohmori Iori 岡山大学, 教育学研究科, 教授 (20403488)
• Co-Investigator(Kenkyū-buntansha): 真下 知士 大阪大学, 医学系研究科, 准教授 (80397554) ; 大内田 守 岡山大学, 医歯薬学総合研究科, 准教授 (80213635)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 急性脳症 / けいれん重積

Outline of Final Research Achievements

We tried to establish an animal model of acute encephalopathy with convulsive status epilepticus. We used Scn1a mutant rats because SCN1A mutations have been linked to hyperthermia-induced seizure susceptibility and acute encephalopathy with a prolonged seizure in human. We induced seizures with various conditions or by using drugs with a proinflammatory effect. Seizures are evoked in Scn1a mutant rats, however, they did not last more than 30 minutes which are often observed in acute encephalopathy in human. Various behavioral tests and pathological examinations of the brain were conducted after provoked seizures. They showed no cognitive impairment and motor disturbance. Pathological tests exhibited no brain edema nor inflammation.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

けいれん重積型急性脳症の発症メカニズムは不明な点が多く，死亡する症例や，知的障害や運動障害，てんかんなどの後遺症を併発する症例がある。病態解明と新規治療法の開発研究にはモデル動物の確立が欠かせない。SCN1A遺伝子異常をもつ患者では急性脳症の合併が多いが、Scn1a遺伝子変異を持つラットで種々の条件を付加して、モデル作製に努めたが、合併症を有するモデルにはならなかった。人の患者における遺伝子解析などで修飾遺伝子の同定を進め、複合的な因子を持つ動物がモデルとなり得るのかもしれない。