Phenotypic interactions between neutrophils and macrophages/microglia in the pathogenesis of intracerebral hemorrhage

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04673
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kumamoto University
• Principal Investigator: Katsuki Hiroshi 熊本大学, 大学院生命科学研究部(薬), 教授 (40240733)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脳卒中 / 好中球 / ミクログリア / ロイコトリエン / 核内受容体 / トロンビン

Outline of Final Research Achievements

Leukotriene B4 generated within the brain in response to intracerebral hemorrhage (ICH) was found to determine the prognosis by promoting leukocyte infiltration and participating in inflammatory responses and axon tract damage in the brain. In addition, stimulation of ligand-dependent transcription factors such as Nurr1 and aryl hydrocarbon receptor was shown to alleviate pathological events in ICH by inhibiting leukocyte infiltration and/or microglia/macrophage recruitment. Moreover, a novel experimental system using brain slice cultures was developed to give rudimentary findings concerning the dynamics of neutrophil phenotypes associated with ICH.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

十分な治療法の確立されていない脳出血に対し、好中球の浸潤を起点とする脳内炎症応答を抑制することが有効な治療戦略となり得ることを示したのに加え、ロイコトリエンB4受容体、Nurr1、芳香族炭化水素受容体といった新たな治療標的候補分子を具体的に提示した意義は大きい。また、好中球の浸潤は脳出血に限らず多くの脳病態において認められるため、新規に構築した培養実験系は今後多様な疾患の成立機序を解析する上で有効な手段となり得る。