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A novel therapeutic strategy for postoperative cognitive dysfunction by PGC-1a and microRNA

Research Project

Project/Area Number 17K16737
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionKochi University

Principal Investigator

Tateiwa Hiroki  高知大学, 教育研究部医療学系臨床医学部門, 助教 (90614397)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords術後認知機能障害 / neuroimflammation / αリポ酸 / BDNF / POCD / ALA / PGC-1α / neuroinflammation / rt-PCR / PGC1-α / microRNA
Outline of Final Research Achievements

Postoperative cognitive dysfunction (POCD) is caused by the neuroinflammation due to surgical invasion. This condition is generally associated with postoperative QOL deterioration. Recent research suggested that preoperative exercise may be an effective preventive strategy. However, the preoperative exercise approach is often difficult to implement in elderly patients. In this study, we examined whether POCD could be prevented by administering ALA, a substance that induces the protein PGC-1α expressed during exercise.
As a result, PGC-1α and hippocampal BDNF levels increased by preoperatively administering ALA to aged rats. In addition, the novel object recognitive test on POD7 showed that cognitive function was maintained. Furthermore, hippocampal TNF-α levels decreased.
ALA administration suppressed neuroinflammation and prevented the development of POCD.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の進行および手術技術の向上に伴い、高齢患者が手術を受ける機会が増加している。それに伴い術後認知機能障害(POCD)などの合併症が社会的にも大きな問題となっている。POCDに対して術前の運動が有効である可能性は示唆されているものの、特に高齢患者では困難な場合も少なくない。それに対してαリポ酸の投与により、運動と同等の効果をもたらす可能性がある今研究結果がもたらす意味は大きいと思われる。またαリポ酸はサプリメントとしてもヒトでも使用されているものであり、今後、臨床への応用が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] The role of hippocampal brain-derived neurotrophic factor in age-related differences in neuropathic pain behavior in rats.2018

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

      Life Sciences

      Volume: 197 Pages: 56-66

    • DOI

      10.1016/j.lfs.2018.01.030

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 高次脳機能に対する周術期アプローチ - 最新ガイドラインから読み解く予防・治療法.2019

    • Author(s)
      立岩浩規
    • Organizer
      日本区域麻酔学会 第6回学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 高齢者の術後認知機能障害:防止対策 基礎研究からのアプローチ2018

    • Author(s)
      立岩浩規、河野崇、横山正尚
    • Organizer
      日本麻酔科学会 第65回学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 神経麻酔アップデート: 術後認知異常.2018

    • Author(s)
      立岩浩規
    • Organizer
      日本臨床麻酔学会 第38回大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Age-related anatomical changes of spinal nerves and its application to the neuropathic pain model in rat2017

    • Author(s)
      Hiroki Tateiwa, Takashi Kawano, Masataka Yokoyama
    • Organizer
      European Society of Anaesthesiology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラット脊髄神経解剖の加齢性変化と神経障害性痛モデルへの応用2017

    • Author(s)
      立岩 浩規, 河野 崇,青山 文,山中 大樹,西垣 厚,横山 正尚
    • Organizer
      日本麻酔科学会第65回学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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