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Pathophysiological investigation of cytokines and chemokines playing a role in the mechanism of developing brain edema

Research Project

Project/Area Number 18K17417
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionWakayama Medical University

Principal Investigator

Mitsunori OZAKI  和歌山県立医科大学, 医学部, 博士研究員 (00760521)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords脳浮腫 / サイトカイン / 水中毒 / アクアポリン1 / 脈絡叢 / 免疫染色 / CX3CR1 / 急性心不全 / ノックアウトマウス / 低ナトリウム血症 / アクアポリン
Outline of Final Research Achievements

Water intoxication causes excessive intracellular water retention and develops crucial complication such as brain edema. The aim of the present study is to establish the diagnostic criteria related to cytokines and chemokines for water intoxication in molecular forensic medicine. In this study, it was clarified that the signal mediated by IFN-γ and CX3CR1 functions protectively against cerebral edema, but its molecular mechanism has not been clarified. However, we found that gene expression in the choroid plexus of aquaporin 1 and 4, water channels, was significantly altered in water intoxication, which suggests that the aquaporin 1/4 ratio may be a new indicator of water intoxication death. Since the phenotypes of both gene-deficient mice are clear, we plan to continue exploring the molecular mechanism of protection of cerebral edema by both molecules.

Academic Significance and Societal Importance of the Research Achievements

水中毒に関連する分子レベルでの法医診断基準の確立は急務であると考えられている。水中毒による脳浮腫に対してIFN-γ、CX3CR1を介したシグナルが保護的に機能し水チャネルの遺伝子発現の変化が死亡率に影響を及ぼすことを解明した本研究は、法医学実務に応用が効く知見を提供したと考えられる。脳内での水チャネルを制御する機構は解明されていない点が多く、脳浮腫制御に関連するサイトカインを同定できた学術的意義は少なくない。また、脳浮腫の発生機序に関連するサイトカイン、ケモカインの病態生理学的役割を解明することは、脳浮腫の分子標的治療にも応用できる可能性を秘めており臨床医学分野への貢献も期待できるものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Crucial Involvement of IL-6 in Thrombus Resolution in Mice via Macrophage Recruitment and the Induction of Proteolytic Enzymes.2020

    • Author(s)
      Nosaka M, Ishida Y, Kimura A, Kuninaka Y, Taruya A, Ozaki M, Tanaka A, Mukaida N, Kondo T
    • Journal Title

      Front Immunol

      Volume: - Pages: 3150-3150

    • DOI

      10.3389/fimmu.2019.03150

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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