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Elucidation of neuroinflammatory mechanisms linking general anesthesia

Research Project

Project/Area Number 18H02898
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionKochi University

Principal Investigator

Kawano Takashi  高知大学, 教育研究部医療学系臨床医学部門, 教授 (40380076)

Co-Investigator(Kenkyū-buntansha) 村田 和子  高知大学, 教育研究部医療学系臨床医学部門, 講師 (50325429)
高橋 章  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (90304047)
宮武 加苗  高知大学, 教育研究部医療学系臨床医学部門, 助教 (10380362)
横山 正尚  高知大学, 教育研究部医療学系臨床医学部門, 教授 (20158380)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywords術後せん妄 / 脳内神経炎症 / 術後認知機能障害 / ミクログリア / 術後神経認知異常
Outline of Final Research Achievements

Animal research was conducted to elucidate the pathological mechanism of postoperative delirium (POD), and the following points were clarified. (1) An animal model of POD was established using laparotomy and trace fear conditioning tasks. (2) Acute neuroinflammation plays an important role in the pathological mechanism of POD. (3) Chronification of acute neuroinflammation is the cause of worsening postoperative cognitive outcome. (4) Aging is a key factor in the chronicity of neuroinflammation in the brain. (5) The hippocampus and prefrontal cortex are particularly vulnerable to age-related neuroinflammation.
These findings imply that interventions targeting the neuroinflammation may be useful in considering preventive and therapeutic strategies for postoperative cognitive disorders, including POD.

Academic Significance and Societal Importance of the Research Achievements

術後せん妄 (Postoperative delirium: POD) は、高齢手術患者において頻度が高く、退院後のQOL低下や就労困難のみならず、死亡率増加にも関連する。PODの危険因子は、高齢であることが一貫して報告されているが、現時点において科学的根拠の高い予防・治療方法はない。
本研究ではこれまでになかったPODの動物モデルを確立した。このモデルによりPODの病態機序の解明が前進すると考えられる。我々はこのモデルを用いてPODの病態に脳内神経炎症が重要な役割を果たすことを明らかとした。今後、脳内神経炎症を標的とした新規の予防・治療法の開発が期待される。

Report

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

    (6 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats2019

    • Author(s)
      Koyama T, Kawano T, Iwata H, Aoyama B, Eguchi S, Nishigaki A, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Locatelli FM, Yokoyama M
    • Journal Title

      J Anesth

      Volume: 33 Issue: 3 Pages: 482-486

    • DOI

      10.1007/s00540-019-02635-3

    • NAID

      40021917789

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute and Long-Term Effects of Haloperidol on Surgery-Induced Neuroinflammation and Cognitive Deficits in Aged Rats2019

    • Author(s)
      Nishigaki A, Kawano T, Iwata H, Aoyama B, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Eguchi S, Locatelli FM, Yokoyama M
    • Journal Title

      J Anesth

      Volume: 33 Issue: 3 Pages: 416-425

    • DOI

      10.1007/s00540-019-02646-0

    • NAID

      40021917728

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats.2018

    • Author(s)
      Aoyama B, Kawano T, Iwata H, Nishigaki A, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Eguchi S, Locatelli FM, Yokoyama M
    • Journal Title

      J Pharmacol Sci

      Volume: 139 Issue: 2 Pages: 77-83

    • DOI

      10.1016/j.jphs.2018.11.009

    • NAID

      120006941132

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats2018

    • Author(s)
      Locatelli FM, Kawano T, Iwata H, Aoyama B, Eguchi S, Nishigaki A, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Yokoyama M.
    • Journal Title

      J Pharmacol Sci

      Volume: 137 Issue: 4 Pages: 395-402

    • DOI

      10.1016/j.jphs.2018.08.006

    • NAID

      120006941131

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高齢者の認知機能2020

    • Author(s)
      河野 崇
    • Organizer
      第 32 回日本老年麻酔学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 急性脳内神経炎症およびせん妄様行動に及ぼす急性術後痛の関与 -ラット開腹手術モデルでの検討-2018

    • Author(s)
      小山 毅、山中 大樹、青山 文、立岩 浩規、河野 崇、横山 正尚
    • Organizer
      日本麻酔科学会 中国・四国支部第55回学術集会
    • Related Report
      2018 Annual Research Report

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

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