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Clarification of a mechanism of removing metabolic waste in the brain by interstitial fluid flow

Research Project

Project/Area Number 20H04504
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionKyoto Institute of Technology (2023)
Osaka University (2020-2022)

Principal Investigator

Naoki Takeishi  京都工芸繊維大学, 機械工学系, 准教授 (30787669)

Co-Investigator(Kenkyū-buntansha) 横山 直人  東京電機大学, 工学部, 教授 (80512730)
田中 壽  大阪大学, 医学系研究科, 教授 (40294087)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords脈波 / 脳脊髄液 / 脳動脈 / 流体力学 / 計算バイオメカニクス / 赤血球 / 微小循環 / 脳間質液 / 物質輸送 / 脳動脈網 / 血管周囲腔 / 代謝 / 脳内老廃物
Outline of Research at the Start

脳内老廃物の除去機構の一つとして、脳間質液の重要性が指摘されてきたが、その詳細な動態は未だ明らかにされていない。組織スケールでのタンパク質の輸送と沈着のダイナミクスの理解は、アルツハイマー病をはじめとする脳疾患の進行機序を説明する上で必要不可欠であるにも関わらず、分子-組織間の階層を繋ぐ解析手法は確立されていない。本研究では、実験データに基づき、分子スケールのタンパク質の凝集と組織スケールにおける間質液流れの階層を繋ぐ計算力学モデルを構築し、脳間質液流れによる脳内老廃物の排除機構が成立する力学的平衡状態やその破綻機序を解明する。この知見に基づき、脳疾患の進行機序を説明する力学的概念を構築する。

Outline of Final Research Achievements

To clarify the dynamics regarding the removal of metabolic waste in the brain by interstitial fluid flow and constructing a mechanical concept that explains the progression mechanism of brain diseases, we conducted research on mathematical models and numerical simulations based on experimental measurement. Our numerical results showed the net CSF flow velocity collapses on the analytical solution derived from the lubrication theory in analogy with Taylor’s swimming sheet. Next, we performed numerical simulations of the the arterial pulsation in whole-scale cerebral arteries, constructed based on the medical image data, using one-dimensional mode, and successfully estimated aforementioned arterial pulsation in microvessels. These numerical results will serve as fundamental knowledge for modeling arterial-pulsation dependent CSF flow, and provide insight into a mechanism of removing metabolic waste in the brain by interstitial fluid flow.

Academic Significance and Societal Importance of the Research Achievements

本研究により,脈波動態から脳内老廃物除去機構と密接に関わる脳脊髄液流れの流速を推定できることを示した.これは,脈波動態が脳内老廃物除去において生理学的重要な役割を担うことを示唆する.これらの知見は,脳内老廃物に関する除去機能や異常な蓄積の推定を目的とした,新たらしい脳内脈波計測技術の構築や脳機能計測機器の開発戦略に繋がる.

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (50 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 3 results) Presentation (27 results) (of which Int'l Joint Research: 12 results,  Invited: 2 results) Book (2 results) Remarks (7 results)

  • [Int'l Joint Research] Politecnico di Torino(イタリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] スウェーデン王立工科大学(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Viscoelasticity of suspension of red blood cells under oscillatory shear flow2024

    • Author(s)
      Takeishi Naoki、Rosti Marco Edoardo、Yokoyama Naoto、Brandt Luca
    • Journal Title

      Physics of Fluids

      Volume: 36 Issue: 4

    • DOI

      10.1063/5.0196272

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Numerical analysis of viscoelasticity of two-dimensional fluid membranes under oscillatory loadings2024

    • Author(s)
      Takeishi Naoki、Santo Masaya、Yokoyama Naoto、Wada Shigeo
    • Journal Title

      Results in Engineering

      Volume: 22 Pages: 102304-102304

    • DOI

      10.1016/j.rineng.2024.102304

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced axial migration of a deformable capsule in pulsatile channel flows2023

    • Author(s)
      Takeishi Naoki、Rosti Marco Edoardo
    • Journal Title

      Physical Review Fluids

      Volume: 8 Issue: 6

    • DOI

      10.1103/physrevfluids.8.l061101

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Airway performance in infants with congenital tracheal stenosis associated with unilateral pulmonary agenesis: effect of tracheal shape on energy flux2022

    • Author(s)
      Kageyama Shiori、Takeishi Naoki、Harada Naoki、Taniguchi Kao、Morita Keiichi、Wada Shigeo
    • Journal Title

      Medical & Biological Engineering & Computing

      Volume: 60 Issue: 8 Pages: 2335-2348

    • DOI

      10.1007/s11517-022-02601-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluid dynamic assessment of positive end-expiratory pressure in a tracheostomy tube connector during respiration2022

    • Author(s)
      Kageyama Shiori、Takeishi Naoki、Taenaka Hiroki、Yoshida Takeshi、Wada Shigeo
    • Journal Title

      Medical & Biological Engineering & Computing

      Volume: 60 Issue: 10 Pages: 2981-2993

    • DOI

      10.1007/s11517-022-02649-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of cardiac function using the modified ejection fraction as an indicator of myocardial circumferential strain2022

    • Author(s)
      MORISHITA Takaomi、TAKEISHI Naoki、II Satoshi、WADA Shigeo
    • Journal Title

      Journal of Biomechanical Science and Engineering

      Volume: 17 Issue: 2 Pages: 22-00014-22-00014

    • DOI

      10.1299/jbse.22-00014

    • ISSN
      1880-9863
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Computational fluid dynamics assessment of congenital tracheal stenosis2022

    • Author(s)
      Morita Keiichi、Takeishi Naoki、Wada Shigeo、Hatakeyama Tadashi
    • Journal Title

      Pediatric Surgery International

      Volume: 38 Issue: 12 Pages: 1769-1776

    • DOI

      10.1007/s00383-022-05228-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inertial migration of red blood cells under a Newtonian fluid in a circular channel2022

    • Author(s)
      Takeishi Naoki、Yamashita Hiroshi、Omori Toshihiro、Yokoyama Naoto、Wada Shigeo、Sugihara-Seki Masako
    • Journal Title

      Journal of Fluid Mechanics

      Volume: 952 Pages: 952-952

    • DOI

      10.1017/jfm.2022.936

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Left Ventricular Hypertrophy and Myocardial Stiffness on Myocardial Strain Under Preserved Ejection Fraction2021

    • Author(s)
      Morishita Takaomi、Takeishi Naoki、Ii Satoshi、Wada Shigeo
    • Journal Title

      Annals of Biomedical Engineering

      Volume: 49 Issue: 7 Pages: 1670-1687

    • DOI

      10.1007/s10439-020-02706-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cerebrospinal fluid flow driven by arterial pulsations in axisymmetric perivascular spaces: analogy with Taylor’s swimming sheet2021

    • Author(s)
      Yokoyama Naoto、Takeishi Naoki、Wada Shigeo
    • Journal Title

      Journal of Theoretical Biology

      Volume: in press Pages: 110709-110709

    • DOI

      10.1016/j.jtbi.2021.110709

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation2021

    • Author(s)
      Takeishi Naoki、Shigematsu Taiki、Enosaki Ryogo、Ishida Shunichi、Ii Satoshi、Wada Shigeo
    • Journal Title

      Journal of The Royal Society Interface

      Volume: 18 Issue: 184 Pages: 20210554-20210554

    • DOI

      10.1098/rsif.2021.0554

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Axial and Nonaxial Migration of Red Blood Cells in a Microtube2021

    • Author(s)
      Takeishi Naoki、Yamashita Hiroshi、Omori Toshihiro、Yokoyama Naoto、Sugihara-Seki Masako
    • Journal Title

      Micromachines

      Volume: 12 Issue: 10 Pages: 1162-1162

    • DOI

      10.3390/mi12101162

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Numerical analysis of cellular flows spanning single red blood cell dynamics to bulk suspension rheology2023

    • Author(s)
      Naoki Takeishi
    • Organizer
      ASME-JSME-KSME Joint Fluids Engineering Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Numerical analysis of suspension rheology of red blood cells under oscillatory shear flow2023

    • Author(s)
      Naoki Takeishi, Marco Edoardo Rosti, Naoto Yokoyama, Luca Brandt
    • Organizer
      76th Annual Meeting of the Division of Fluid Dynamics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Numerical analysis of the lateral movement of a deformable spherical capsule in pulsatile channel flows2023

    • Author(s)
      Naoki Takeishi, Marco Edoardo Rosti
    • Organizer
      The 3rd World Congress of ESCHM-ISB-ISCH2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 振動せん断流れ場における赤血球懸濁液の粘弾性解析2023

    • Author(s)
      武石直樹, Marco Edoardo Rosti, 横山直人, Luca Brandt.
    • Organizer
      日本流体力学会年会2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] 管路内振動流場におけるカプセルの軸集中現象に関する数値解析2023

    • Author(s)
      武石直樹, Marco Edoardo Rosti
    • Organizer
      日本機械学会2023年度年次大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 膜-流体連成解析による赤血球懸濁液の粘弾性解析2023

    • Author(s)
      武石直樹, Marco E Rosti, 横山直人, Luca Brandt
    • Organizer
      第46回日本バイオレオロジー学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Numerical analysis of the lateral movement of red blood cells in circular microchannels2022

    • Author(s)
      Naoki Takeishi, Hiroshi Yamashita, Naoto Yokoyama, Masako Sugihara-Seki
    • Organizer
      15th Wold Congress on Computational Mechanics & 8th Asian Pacific Congress on Computational Mechanics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Numerical analysis and modeling of suspension rheology of red blood cells2022

    • Author(s)
      Naoki Takeishi, Marco E. Rosti, Naoto Yokoyama, Luca Brandt
    • Organizer
      9th World Congress of Biomechanics 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Axial and nonaxial migration of red blood cells under a Newtonian fluid in microchannels2022

    • Author(s)
      Naoki Takeishi, Hiroshi Yamashita, Toshihiro Omori, Naoto Yokoyama, Masako Sugihara-Seki
    • Organizer
      th World Congress of Biomechanics 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 円管路内における赤血球の慣性移動に関する数値解析2022

    • Author(s)
      武石直樹, 山下博士, 大森俊宏, 横山直人, 和田成生, 関眞佐子
    • Organizer
      日本流体力学会年会2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] 2次元流体膜モデルを用いた振動圧力下における脂質二重膜の動的粘弾性解析2022

    • Author(s)
      武石直樹, 山頭雅也, 横山直人, 和田成生
    • Organizer
      日本機械学会2022年度年次大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 慣性効果による赤血球の円管路断面内の移動に関する数値解析2022

    • Author(s)
      武石直樹, 山下博士, 横山直人, 関眞佐子
    • Organizer
      第66回理論応用力学講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胸部大動脈ステント留置・バイパス接続による流路変更に伴う頸部血管系の脈波伝ぱを考慮した血流動態解析2022

    • Author(s)
      李佳龍,武石直樹,田中壽,和田成生.
    • Organizer
      日本機械学会第32回バイオフロンティア講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自発呼吸を考慮した三次元呼吸回路デバイス内の数値流体解析と 呼気終末陽圧評価2022

    • Author(s)
      蔭山紫織, 武石直樹, 妙中浩紀,吉田健史,和田成生
    • Organizer
      日本機械学会第32回バイオフロンティア講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 無針注射を想定した薬液の高速射出の数値解析:真皮層内の分布予測2022

    • Author(s)
      千田衣織, 武石直樹, 大谷智仁, 和田成生
    • Organizer
      日本機械学会関西学生会2021年度卒業研究発表講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] メゾスコピックモデルによるフィブリン凝集塊の力学特性の評価2022

    • Author(s)
      大島直丈, 武石直樹, 大谷智仁, 和田成生
    • Organizer
      日本機械学会関西学生会2021年度卒業研究発表講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Suspension rheology of red blood cells under oscillatory shear flow2021

    • Author(s)
      Naoki Takeishi, Marco E Rosti, Naoto Yokoyama, Shigeo Wada, Luca Brandt.
    • Organizer
      ESCHM-ISCH-ISB 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Stability of a red blood cell in a narrow rectangular microchannel2021

    • Author(s)
      Naoki Takeishi, Hiroaki Ito, Shigeo Wada.
    • Organizer
      25th ICTAM2020+1
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Numerical analysis of the inertial migration of the red blood cell in a channel2021

    • Author(s)
      Naoki Takeishi, Hiroshi Yamashita, Naoto Yokoyama, Masako Sugihara-Seki, Shigeo Wada.
    • Organizer
      ESCHM-ISCH-ISB 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 振動流下における赤血球濃厚懸濁液の数値解析2021

    • Author(s)
      武石直樹, Marco E Rosti, 横山直人, 和田成生, Luca Brandt.
    • Organizer
      日本流体力学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 無心注射による薬剤送達技術の確立に向けた真皮層中の薬液流れの数値解析2021

    • Author(s)
      武石直樹, 堀川健介, 横山直人, 和田成生.
    • Organizer
      日本機械学会2021年度年次大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 片肺欠損を伴う先天性気管狭窄患者の気管内気流解析と評価2021

    • Author(s)
      武石直樹, 蔭山紫織, 谷口香緒, 森田圭一, 和田成生.
    • Organizer
      第29回バイオフィジオロジー研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Numerical analysis of lipid bilayer under oscillatory deformation using 2D fluid membrane model2021

    • Author(s)
      Masaya SANTOU, Naoki TAKEISHI, Naoto YOKOYAMA, Tomohiro Ohtani, Shigeo WADA
    • Organizer
      The 11th Asian-Pacific Conference on Biomechanics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 二次元流体膜モデルを用いた脂質二重膜の粘弾性評価2021

    • Author(s)
      山頭 雅也, 横山 直人, 武石 直樹, 大谷 智仁, 和田 成生
    • Organizer
      日本流体力学会年会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] DEVELOPMENT OF A COMPUTATIONAL PLATFORM TO EVALUATE A POSITIVE END-EXPIRATORY PRESSURE IN POSTOPERATIVE PATIENTS WITH TRACHEOSTOMY2021

    • Author(s)
      S. Kageyama, N. Takeishi, H. Taenaka, T. Yoshida, S. Wada
    • Organizer
      Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Numerical analysis of airflow in abnormal curved trachea2020

    • Author(s)
      Naoki Takeishi, Naoki Harada, Shiori Kageyama, Keiichi Morita, Shigeo Wada.
    • Organizer
      Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C2020 Virtual Conference)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 真皮層における射出薬液の分布予測にむけた計算力学モデルの開発2020

    • Author(s)
      武石直樹, 堀川健介, 和田成生.
    • Organizer
      日本機械学会2020年度年次大会(web講演会)
    • Related Report
      2020 Annual Research Report
  • [Book] 医用工学ハンドブック2022

    • Author(s)
      佐久間 一郎、秋吉 一成、津本 浩平
    • Total Pages
      544
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437350
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Book] 医療に活かす生体医工学2020

    • Author(s)
      日本生体医工学会、平田 雅之、齋藤 充弘、紀ノ岡 正博、和田 成生、伊井 仁志、大谷 智仁、武石 直樹、橋爪 誠、大城 理、岡山 慶太、坂田 泰史、河野 喬仁、村田 正治、佐久間 一郎、篠原 一彦、江藤 正俊、小林 聡、牟田口 淳、今田 憲二郎、家入 里志、山田 耕嗣、大西 峻、山家 智之、不二門 尚、松村 泰志、野村 泰伸
    • Total Pages
      224
    • Publisher
      コロナ社
    • ISBN
      9784339072471
    • Related Report
      2020 Annual Research Report
  • [Remarks] 個人用ホームページ

    • URL

      http://naoki-takeishi.sakura.ne.jp/jp/home.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] Research map

    • URL

      https://researchmap.jp/ntakeishi

    • Related Report
      2023 Annual Research Report
  • [Remarks] Google Scholar

    • URL

      https://scholar.google.co.jp/citations?user=rp9h9WQAAAAJ&hl=ja#

    • Related Report
      2023 Annual Research Report
  • [Remarks] ResearchGate

    • URL

      https://www.researchgate.net/profile/Naoki-Takeishi

    • Related Report
      2023 Annual Research Report
  • [Remarks] 個人ホームページ

    • URL

      http://naoki-takeishi.sakura.ne.jp/jp/home.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 個人ウェブサイト

    • URL

      http://naoki-takeishi.sakura.ne.jp/jp/home.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 個人用webサイト

    • URL

      http://naoki-takeishi.sakura.ne.jp/jp/home.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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