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Elucidation of the pathogenesis of postoperative delirium using axonal injury markers and development of preventive and method of treatment.

Research Project

Project/Area Number 20K17831
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Inoue Reo  東京大学, 医学部附属病院, 助教 (10845267)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords術後せん妄 / pNF-H / 血清バイオマーカー / pNF‐H / バイオマーカー / せん妄重症度
Outline of Research at the Start

術後せん妄について神経軸索傷害マーカー(pNF-H)を主軸にした血液学的診断法(感度・特異度)と重症度の定量的評価法を開発する。また血清中のpNF-H値が術後認知機能との関連も検討する。さらにpNF-Hに加えて炎症、血液-脳関門(血管内皮)傷害、認知症と関連が深いアポリポ蛋白質との相互作用の観点から術後せん妄の病態を解明し、せん妄や術後認知機能障害の予防・治療法開発の創薬標的を探索する。

Outline of Final Research Achievements

By measuring and comparing pNF-H measurements over time, we clarified the usefulness of pNF-H in delirium diagnosis and the correspondence with the clinical features of delirium. brain dysfunction. Specifically, we revealed that several vascular endothelial adhesion factors that regulate migration of inflammatory cells to the central nervous system at the blood-brain barrier are associated with the onset and severity of central nervous system damage.
In addition, we found that the odds ratio of postoperative delirium development increased in patients with increased pNF-H levels before surgery, and that the risk of developing delirium increased with age and preoperative pNF-H, with a sensitivity of 70% and a specificity of 91%. The usefulness as a diagnostic marker that can be predicted by % was also shown. Therefore, measuring pNF-H can be a biomarker for CNS protective strategies in the acute postoperative period to prevent the development of delirium and higher brain dysfunction.

Academic Significance and Societal Importance of the Research Achievements

上述のように術後せん妄とpNF-Hの関連について明らかにしたことにより、精神症状を血液検査で診断することに繋がり国際的にみても画期的な成果といえる。本研究は高い新規性が提案でき、また神経障害を背景とする術後以外のせん妄・認知機能障害(がん化学療法や放射線療法によって発症し、遷延化することのあるがん治療後の認知機能障害)においてもpNF-H測定の有用性の可能性を示すものである。本研究を経て我々は臨床患者を対象として脳認知機能および神経傷害についてpNF-Hを用いた病態解明に継続的に取り組み、十分な研究体制を構築するに至っている。今後はこの体制を生かし、様々な方面への応用を期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Elevation of serum plasminogen activator inhibitor-1 predicts postoperative delirium independent of neural damage: a sequential analysis2022

    • Author(s)
      Mietani Kazuhito、Hasegawa-Moriyama Maiko、Yagi Koichi、Inoue Reo、Ogata Toru、Shimojo Nobutake、Seto Yasuyuki、Uchida Kanji、Sumitani Masahiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17091-17091

    • DOI

      10.1038/s41598-022-21682-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum levels of apolipoprotein A-I and E are associated with postoperative delirium: A post hoc analysis2022

    • Author(s)
      Mietani K, Hasegawa-Moriyama M, Inoue R, Ogata T, Shimojo N, Kurano M, Yatomi Y, Uchida K, Sumitani M.
    • Journal Title

      Medicine

      Volume: 102 Issue: 30 Pages: e29906-e29906

    • DOI

      10.1097/md.0000000000029906

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2020-04-28   Modified: 2024-01-30  

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