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Neutrophil extracellular traps contribute multiple organ failure after traumatic brain injury

Research Project

Project/Area Number 21K17324
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Kawai Chihiro  京都大学, 医学研究科, 助教 (40894754)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords法医病理学 / 頭部外傷 / 法医病理
Outline of Research at the Start

本研究では、頭部外傷に続発する多臓器障害への好中球細胞外トラップの関与を解明することを目的とする。頭部外傷の予後規定因子の一つに肺など遠隔臓器に続発する多臓器障害がある。生体防御機構である好中球細胞外トラップ(以下 NETs)は頭部外傷の神経予後に関与し、外傷の重症度と血中発現量が相関する。一方で、NETsは敗血症や腫瘍性病変などで過剰に発現し、多臓器障害を引き起こす。しかし、これまでに頭部外傷に続発する多臓器障害の進展にこのNETsが関与しているかは明らかにされていない。本研究ではモデルマウスと分子病態学的な手法を用いてこの病態関連を解明する。

Outline of Final Research Achievements

The mechanism through which traumatic brain injury (TBI) results in multiple organ injuries remains unclear. In this study, we used mouse models to investigate the pathological changes that occur in various organs following life-threatening TBI, with a focus on the role of damage-associated molecular patterns (DAMPs) such as neutrophil extracellular traps (NETs) and high-mobility group box 1 (HMGB1) in peripheral organs. Our findings suggest that during the acute phase following TBI, inflammation spreads to peripheral organs, while the disruption of neuromodulatory mechanisms contributes to organ damage in the subacute phase. Although NETs were observed in the brain-injured area, no systemic effects were detected. Conversely, HMGB1 displayed opposing functions in the central and peripheral regions, exacerbating inflammation in the brain-injured area while acting as an inflammation suppressor in other organs during the acute phase.

Academic Significance and Societal Importance of the Research Achievements

近年、HMGB1は頭部外傷に対する新たな治療標的として着目されている。しかしながら、本研究により外傷性脳損傷において、HMGB1は相反する機能を有していることが示唆された。新たな治療法の確立には、損傷局所に留まらず、全身の詳細な評価が必要であることを再認識させる。また、HMGB1は未だ機序が不明確な脳損傷誘導性末梢免疫抑制機構に寄与している可能性があり、今後はマクロファージを起点とした外傷時の末梢免疫制御機構を解明し、末梢臓器への影響から見た新たな予防・治療法の確立に貢献したい。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2024 2023 2022

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] Fatal cardiac dysfunction in a child with Williams syndrome2024

    • Author(s)
      Kawai Chihiro、Kondo Hidehito、Miyao Masashi、Sunada Mariko、Ozawa Seiichiro、Kotani Hirokazu、Minami Hirozo、Nagai Hideki、Abiru Hitoshi、Yamamoto Akira、Tamaki Keiji、Nishitani Yoko
    • Journal Title

      Legal Medicine

      Volume: 67 Pages: 102387-102387

    • DOI

      10.1016/j.legalmed.2023.102387

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systemic amyloidosis with amyloid goiter: an autopsy report.2023

    • Author(s)
      Kawai C, Miyao M, Kotani H, Minami H, Abiru H, Hamayasu H, Yamamoto A, Tamaki K.
    • Journal Title

      Legal Medicine

      Volume: - Pages: 102167-102167

    • DOI

      10.1016/j.legalmed.2022.102167

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fatal Dieulafoy lesion with IgG4-related disease: an autopsy case report.2022

    • Author(s)
      Miyao M, Kawai C, Kotani H, Minami H, Abiru H, Hamayasu H, Yamamoto A, Tamaki K.
    • Journal Title

      Legal Medicine

      Volume: - Pages: 102059-102059

    • DOI

      10.1016/j.legalmed.2022.102059

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial fission in hepatocytes as a potential therapeutic target for nonalcoholic steatohepatitis2022

    • Author(s)
      Miyao M, Kawai C, Kotani H, Minami H, Abiru H, Hamayasu H, Eguchi S, Tamaki K.
    • Journal Title

      Hepatology Research

      Volume: - Issue: 12 Pages: 1020-1033

    • DOI

      10.1111/hepr.13832

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 外傷性脳損傷に対する抗HMGB1抗体療法が末梢諸臓器へもたらす影響評価2024

    • Author(s)
      川合千裕, 宮尾 昌, 南 博蔵, 長井 秀樹, 阿比留仁, 玉木敬二, 西谷陽子.
    • Organizer
      第108次日本法医学会学術全国集会.
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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