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Reconsideration of active therapeutics of septic enephalopathy by non-invasive methods focusing on molecular mechanism

Research Project

Project/Area Number 17H04364
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionDoshisha University (2018-2021)
Osaka University (2017)

Principal Investigator

Imamura Yukio  同志社大学, 研究開発推進機構, 学術研究員 (90447954)

Co-Investigator(Kenkyū-buntansha) 松浦 裕司  大阪大学, 医学部附属病院, 医員 (10791709)
村上 由希  関西医科大学, 医学部, 助教 (50580106)
小倉 裕司  大阪大学, 医学系研究科, 准教授 (70301265)
神 隆  国立研究開発法人理化学研究所, 生命システム研究センター, チームリーダー (80206367)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords敗血症性脳症 / 海馬 / タンパク質 / 網羅的統合解析 / 質量分析 / 量子ドット
Outline of Final Research Achievements

Septic encephalopathy is a brain symptom which is caused in severe sepsis survivors. The symptoms contain coma, derilium and cognitive dysfunctions. In this study, we explore the potential active therapeutic intervention. Using a mouse model of septic encephalopathy, we developed the novel method for non-invasive stimulation of vagus nerve and test the validity for the therapeutics. We found that our method was useful to recover the following results: cytokine level, regulatory factor of lymphocyte, survival rates, body temperature, locomotor activity, hippocampal brain activity patterns. Our novel findings suggest the novel therapeutic potential for the medical treatment of the septic encephalopathy patients.

Academic Significance and Societal Importance of the Research Achievements

敗血症性脳症は、現時点では有用な積極的治療介入方法は確立していない。研究代表者らはこの点について、5年に及ぶ研究を遂行した。すなわち、敗血症性脳症ではその発症に関わる因子(DAMPs,PAMPsなど)が極めて多く、多因子疾患である。脳における症候もびまん性であり、部位特異的な治療介入から効果を得るのは難しい。神経可塑性の異常が起こることから自然治癒的な変化を期待することも難しい。本研究で用いた非侵襲的迷走神経刺激療法はまさにこれらの弱点をうまく克服した上で挑戦を試みた治療法であり、人への臨床応用は十分可能であると考えられるが、部検脳など患者さんやご家族の協力が今後の研究発展に必要である。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (24 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Amyloids facilitate DNA transfection in vivo2022

    • Author(s)
      Imamura Yukio、Hiyama Akiko、Miyazaki Haruko、Yamanaka Tomoyuki、Nukina Nobuyuki
    • Journal Title

      Neuroscience Research

      Volume: S0168-0102 Pages: 78-5

    • DOI

      10.1016/j.neures.2022.03.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal immune activation related to neurodevelopmental disorder‐like phenotype in mouse models2021

    • Author(s)
      村上 由希、今村 行雄、酒井 大輔、小西 行郎
    • Journal Title

      Japanese Journal of Biological Psychiatry

      Volume: 32 Issue: 3 Pages: 120-123

    • DOI

      10.11249/jsbpjjpp.32.3_120

    • NAID

      130008091888

    • ISSN
      2186-6465, 2186-6619
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites2021

    • Author(s)
      Murakami Yuki、Imamura Yukio、Kasahara Yoshiyuki、Yoshida Chihiro、Momono Yuta、Fang Ke、Nishiyama Toshimasa、Sakai Daisuke、Konishi Yukuo
    • Journal Title

      International Journal of Tryptophan Research

      Volume: 14 Pages: 1-22

    • DOI

      10.1177/11786469211026639

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds2020

    • Author(s)
      Kasahara Junya、Imamura Yukio、Hiyama Akiko、Yamanaka Tomoyuki、Miyazaki Haruko、Nukina Nobuyuki
    • Journal Title

      Neuroscience Research

      Volume: 20 Pages: 30494-6

    • DOI

      10.1016/j.neures.2020.11.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 生理指標を用いた空間評価手法に関する基礎的研究2020

    • Author(s)
      馬淵, 竜樹、宮崎, 崇文、三浦, 研、三谷, 智子、村上, 由希、今村, 行雄、孔, 相権
    • Journal Title

      日本建築学会中国支部研究報告

      Volume: 43 Pages: 553-556

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker.2019

    • Author(s)
      Murakami Y, Imamura Y, Saito K, Sakai D
    • Journal Title

      Scientific reports

      Volume: 10(1) Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41598-020-60585-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Information Delivery Methods and their Association with Older Adults Memory and Comprehension.2019

    • Author(s)
      Imamura Y, Murakami Y, Mitani S 他6名
    • Journal Title

      Journal of Aging Science

      Volume: 7(2) Issue: 02 Pages: 1-7

    • DOI

      10.35248/2329-8847.19.07.207

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging.2018

    • Author(s)
      F. Zamberlan, L. Turyanska, A. Patane Z. Liu, H. E. L. Williams, M. W. Fay, P. A. Clarke, Yukio Imamura, T. Jin, T. D. Bradshaw, N. R. Thomasa and A. M. Grabowska.
    • Journal Title

      Journal of Material Chemistry B

      Volume: 6 Issue: 4 Pages: 550-555

    • DOI

      10.1039/c7tb02912h

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Generation and Characterization of a Mouse Line Carrying Reck-CreERT2 Knock-In Allele.2018

    • Author(s)
      Tomoko Matsuzaki, Huan Wang, Yukio Imamura, Shunya Kondo, Shuichiro Ogawa, Makoto Noda
    • Journal Title

      Genesis

      Volume: 56(4) Issue: 4

    • DOI

      10.1002/dvg.23099

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Profound haemodynamic response in the prefrontal cortex induced by musical stimuli.2018

    • Author(s)
      Yukio Imamura, Yuki Murakami, Ken Miura, Koji Miura, Takafumi Miyazaki, Keijiro Yamada, Satoko Mitani, Syohken Koh
    • Journal Title

      Journal of Neuroscience and brain imaging

      Volume: 2(1) Pages: 1-13

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions2017

    • Author(s)
      Tashiro T , Murakami Y , Mouri A , Imamura Y, Nabeshima T, Yamamoto, Y , Saito, K
    • Journal Title

      BEHAVIOURAL BRAIN RESEARCH

      Volume: 317 Pages: 279-285

    • DOI

      10.1016/j.bbr.2016.09.050

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 第二光学窓近赤外蛍光プローブによるマウス脳の非侵襲イメージング2017

    • Author(s)
      今村行雄、神隆
    • Journal Title

      BIO INDUSTRY

      Volume: 1 Pages: 7-18

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.2017

    • Author(s)
      Hisatake Matsumoto, Naoya Matsumoto, Junya Shimazaki, Junichiro Nakagawa, Yukio Imamura, Kazuma Yamakawa, Tomoki Yamada, Hiroshi Ogura, Takeshi Shimazu
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12255-12255

    • DOI

      10.1038/s41598-017-12065-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 敗血症性脳症の積極的治療介入方法の探索2021

    • Author(s)
      今村 行雄, 松本 寿健, 松本 直也, 今村 純, 山川 一馬, 吉川 直, 精山 明敏, 村上 由希, 三谷 智子, 中川 淳一郎, 山田 智輝, 室谷 卓, 島崎 淳也, 小倉 裕司, 織田 順, 嶋津 岳士
    • Organizer
      第49回 日本集中治療学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] クラッシュ症候群におけるサイトカインネットワークと臓器障害の関連2020

    • Author(s)
      松本寿健、 小倉裕司 、清水健太郎 、今村行雄 、 嶋津岳士
    • Organizer
      外傷学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] A Critical Risk Factor for a Major Side Effect of Interferon-therapy: Stimulated Indoleamine 2,3-dioxygenase1 is Associated to Depressive States2019

    • Author(s)
      Murakami Y, Imamura Y, Kim HC, Nabeshima T, Saito K
    • Organizer
      ISTRY
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 要介護高齢者を対象とした異なる食事提供プロセスと脳血流変化の関係2018

    • Author(s)
      高木光秀、鈴木大士、宮崎崇文、三浦研、三谷智子、村上由希、今村行雄、孔相権.
    • Organizer
      日本建築学会中国支部研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 要介護高齢者を対象とした異なる食事提供プロセスと表情変化の関係2018

    • Author(s)
      高木光秀、鈴木大士、宮崎崇文、三浦研、三谷智子、村上由希、今村行雄、孔相権.
    • Organizer
      日本建築学会中国支部研究発表会
    • Related Report
      2018 Annual Research Report
  • [Book] Advances in health and disease 302021

    • Author(s)
      Yukio Imamura, Risa Yamano, Yuki Murakami, Ayami Okuzumi, Hisatake Matsumoto
    • Total Pages
      35
    • Publisher
      Nova Science Publisher
    • ISBN
      9781536188561
    • Related Report
      2021 Annual Research Report
  • [Book] From nerve injury to brain inflammatory symptoms: recent findings and imaging technology to evaluate the possible effect of pre-existing nerve injury and neurological symptoms2020

    • Author(s)
      Yukio Imamura, Risa Yamano, Yuki Murakami, Ayami Okuzumi, Hisatake Matsumoto
    • Total Pages
      35
    • Publisher
      Nova Science Publisher
    • ISBN
      9781536188561
    • Related Report
      2020 Annual Research Report
  • [Book] A critical risk factor for a major side effect of interferon-alpha therapy: activated indoleamine 2,3-dioxygenase 1 is related to depressive symptoms2018

    • Author(s)
      Yuki Murakami, Yukio Imamura
    • Total Pages
      18
    • Publisher
      In tech
    • ISBN
      9781789231397
    • Related Report
      2018 Annual Research Report
  • [Book] In vivo imaging of septic encephalopathy.2017

    • Author(s)
      Yukio Imamura, Yuki Murakami, Naoya Matsumoto, Hisatake Matsumoto, Satoko Mitani, Kentaro Shimizu, Hiroshi Ogura, Takeshi Shimazu
    • Total Pages
      19
    • Publisher
      In tech
    • ISBN
      9789535133964
    • Related Report
      2017 Annual Research Report
  • [Book] Deep Tissue Imaging with Linear and Non-linear optics2017

    • Author(s)
      Takashi Jin, Akira Sasaki, Yukio Imamura
    • Total Pages
      27
    • Publisher
      Pan Stanford Publishing
    • ISBN
      9781351797399
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2021

    • Inventor(s)
      貫名信行、今村行雄
    • Industrial Property Rights Holder
      貫名信行、今村行雄
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2017-04-28   Modified: 2023-03-23  

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