Study of pathophysiology of acute encephalopathy in childhood due to fatty acid oxidation disturbance and development of new treatments

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shimane University
• Principal Investigator: Yamaguchi Seiji 島根大学, 学術研究院医学・看護学系, 特任教授 (60144044)
• Research Collaborator: YAMADA Kenji ; FURUI Midori
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 小児急性脳症 / β酸化障害 / 環境温度 / 感染毒素 / 解熱剤 / サイトカイン / タンデムマス / in vitro probe assay

Outline of Final Research Achievements

Acute encephalopathy or sudden infant death are relatively often noted in children with fatty acid oxidation (FAO) disorder. On the other hand, acquired encephalopathy can be caused by infection, intoxication, environmental factor, or metabolic diseases. In this study, relation between the encephalopathy and disturbance of FAO was studied. The results are as follows: 1) heat stress may inhibit FAO, while low temperature might alleviate the FAO disturbance; 2) A toxin of food intoxication may possibly inhibit FAO function; 3) an antipyretic, salicylate (Aspirin), inhibited FAO, while acetaminophen did not; 4) Some cytokines, IL1 or TNFa had an inhibitory effect to FAO, while INFg or IL6 did no effects. It is concluded that acute encephalopathy in childhood could occur through an inhibition of FAO in a considerable number of cases. These findings may be helpful to develop new approaches for prevention or treatments.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

小児は、成人に比べ急性脳症を起こしやすい。急性脳症を起こす要因として考えられている感染、中毒、環境因子、代謝障害などが、β酸化系の障害を介して起こる可能性が示された。小児で急性脳症の起こりやすい要因としてβ酸化系の未発達、脆弱性も考えられる。今回検討した各種要因を今後さらに拡大してβ酸化抑制作用、保護作用の強さを検討する価値が十分にある。
急性脳症の予防、治療開発の方向性として、各病態におけるβ酸化系抑制を防止する対策、すなわち、高温にさらさないこと、解熱剤の選択に注意を払うこと、また特定のサイトカインの抑制薬の開発、β酸化系保護剤の開発などが期待される。