Comprehensive Novel Treatment Strategy for Neonatal Brain Injury via Glial Function Modulation with a Focus on Hypothermia Therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07830
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Aichi Medical University
• Principal Investigator: Kakita Hiroki 愛知医科大学, 医学部, 准教授 (40528949)
• Co-Investigator(Kenkyū-buntansha): 竹下 覚 愛知医科大学, 医学部, 講師 (20715875) ; 山田 恭聖 愛知医科大学, 医学部, 教授 (60405165) ; 青山 峰芳 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (70363918)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 新生児低酸素性虚血性脳症 / グリア / 低体温療法 / エリスロポエチン

Outline of Final Research Achievements

Impact of Glial-Mediated Hypothermia on Neurons and Oligodendrocytes
We revealed that AMP-activated protein kinase (AMPK) is involved in the expression of erythropoietin (EPO) in cultured astrocytes. Furthermore, we demonstrated that this promotion of EPO secretion inhibits neuronal damage. Additionally, in cultured microglia activated by LPS, we elucidated that activation via TRPV4-AMPK-NFkB is suppressed under hypothermic conditions, leading to the inhibition of neuronal injury.
Analysis in HIE Model Rats. t was revealed that some of the inhibition of neuronal damage observed in the above glial cultured cells is also present in HIE model rats.

Free Research Field

新生児学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により新生児低酸素性虚血生脳症の低体温療法を補完する、新規治療法の開発に繋がることが期待される。さらに低体温療法が施行困難で治療法のない早産児の脳室周囲白質軟化症も含めた包括的な新生児脳障害の治療戦略の確立が可能なる。