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Roles of gaseous mediators in the regulation of vascular and neural functions

Research Project

Project/Area Number 16K07066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKeio University

Principal Investigator

KAJIMURA MAYUMI  慶應義塾大学, 医学部(日吉), 教授 (10327497)

Research Collaborator GOTO Shinichi  
MORIKAWA Takayuki  
HISHIKI Takako  
KUBO Akiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords一酸化炭素 / Heme oxygenase / 質量分析イメージング / Neurovascular coupling / エネルギー代謝 / ペナンブラ / コア / diaschisis / ヘムオキシゲナーゼ / 脳血流 / 質量分析 / 血管拡張因子 / 二酸化炭素 / Neurovascular Coupling / ガスバイオロジー / 脳循環代謝
Outline of Final Research Achievements

Brain generates carbon monoxide (CO) via heme oxygenase (HO) reactions. We examined the hypothesis that deletion of HO-2 exacerbates energy metabolism during acute brain ischemia. We conducted quantitative imaging mass spectrometry analysis to decipher local energy metabolism from wild-type (WT) and HO-2-null mice that underwent a 60-min occlusion of the left middle cerebral artery (MCAO). In ipsilateral hemispheres, MCAO caused elevation of AMP, ADP, and lactate, and depletion of ATP in both WT and HO-2 null mice. Ischemic core was larger in HO-2-null than WT mice. Striking differences were found in the contralateral hemispheres, where levels of ADP, AMP and lactate in HO-2-null mice were higher than those in WT mice. It suggests that the HO-2/CO system plays roles in protecting against ischemia not only at ischemic cores where severe reduction of blood flow occurs, but it also protects effectively in trans-hemispheric regions where only a subtle reduction of blood flow takes place.

Academic Significance and Societal Importance of the Research Achievements

研究対象とした脳循環代謝病態においては、ATP産生を支える基質供給機構の同定など、エネルギー代償機転の分子機構の解明が大きな課題である。ガス分子の作用点を代謝物のin vivo-profilingにより空間的・定量的に解析することにより、これまでのin situの系では捉えにくかったセンサー蛋白とシグナル分子の相互作用を、直接的に構築できる可能性を有する点において本研究は独創的である。研究成果は、脳循環障害や神経疾患の病態を理解し、治療のターゲットを絞りこむための布石となりえ、救急蘇生学などの臨床医学研究への波及効果が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016 Other

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway2018

    • Author(s)
      Mashima Kyoko、Takahashi Shinichi、Minami Kazushi、Izawa Yoshikane、Abe Takato、Tsukada Naoki、Hishiki Takako、Suematsu Makoto、Kajimura Mayumi、Suzuki Norihiro
    • Journal Title

      ASN Neuro

      Volume: 10 Issue: 1 Pages: 1-21

    • DOI

      10.1177/1759091418775562

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative imaging mass spectroscopy reveals roles of heme oxygenase-2 for protecting against transhemispheric diaschisis in the brain ischemia2018

    • Author(s)
      1.Shinichi Goto, Takayuki Morikawa, Akiko Kubo, Keiyo Takubo, Keiichi Fukuda, Mayumi Kajimura, Makoto Suematsu
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 63 Issue: 1 Pages: 70-79

    • DOI

      10.3164/jcbn.17-136

    • NAID

      130007387127

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preclinical evaluation of heat-denatured [18F]FDG-labeled red blood cells for detecting splenic tissues with PET in rats2018

    • Author(s)
      2.Yohji Matsusaka, Kazuhiro Takahashi, Yu Iwabuchi, Yuji Ogata, Chiyoko Nishime, Mayumi Kajimura, Masahiro Jinzaki
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 56 Pages: 26-30

    • DOI

      10.1016/j.nucmedbio.2017.09.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 18F-FDG-labelled red blood cell PET for blood-pool imaging: Preclinical evaluation in rats2017

    • Author(s)
      3.Matsusaka Y, Nakahara T, Takahashi K, Iwabuchi Y, Nishime C, Kajimura M, Jinzaki M
    • Journal Title

      EJNMMI Research (European Journal of Nuclear Medicine and Molecular Imaging

      Volume: 19 Issue: 1

    • DOI

      10.1186/s13550-017-0266-3

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart2017

    • Author(s)
      Yuki Sugiura, Yoshinori Katsumata, Motoaki Sano, Kurara Honda, Mayumi Kajimura, Keiichi Fukuda, Makoto Suematsu
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 32361-32361

    • DOI

      10.1038/srep32361

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape2016

    • Author(s)
      Yokouchi M, Atsugi T, Logtestijn MV, Tanaka RJ, Kajimura M, Suematsu M, Furuse M, Amagai M, Kubo A
    • Journal Title

      Elife

      Volume: 5

    • DOI

      10.7554/elife.19593

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cystathionine beta-synthase and PGRMC1 as CO sensors.2016

    • Author(s)
      Kabe Y, Yamamoto T, Kajimura M, Sugiura Y, Koike I, Ohmura M, Nakamura T, Tokumoto Y, Tsugawa H, Handa H, Kobayashi T, and Suematsu M.
    • Journal Title

      Free Radical Biology & Medicine

      Volume: 99 Pages: 333-344

    • DOI

      10.1016/j.freeradbiomed.2016.08.025

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cortical microcirculatory disturbance in the super acute phase of subarachnoid hemorrhage2016

    • Author(s)
      Mami Ishikawa, Mayumi Kajimura, Takayuki Morikawa, Kosuke Tsukada, Toshiyuki Tsuji, Gen Kusaka, Yuichi Tanaka, Makoto Suematsu
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 368 Pages: 326-333

    • DOI

      10.1016/j.jns.2016.06.067

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system2016

    • Author(s)
      Takuya Iizumi, Shinichi Takahashi, Kyoko Mashima, Kazushi Minami, Yoshikane Izawa, Takato Abe, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki
    • Journal Title

      Journal of Neuroinflammation

      Volume: 13 Issue: 1 Pages: 99-99

    • DOI

      10.1186/s12974-016-0564-0

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage2016

    • Author(s)
      Ishikawa M., Kajimura M., Morikawa T., Tsukada K., Tsuji T., Kusaka G., Tanaka Y., Suematsu M.
    • Journal Title

      Acta Neurochirurgica

      Volume: - Issue: 6 Pages: 1057-1067

    • DOI

      10.1007/s00701-016-2792-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CO-CBS-H2 S Axis: From Vascular Mediator to Cancer Regulator.2016

    • Author(s)
      Suematsu M, Nakamura T, Tokumoto Y, Yamamoto T, Kajimura M, Kabe Y.
    • Journal Title

      Microcirculation

      Volume: 23 Issue: 3 Pages: 183-190

    • DOI

      10.1111/micc.12253

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Protective roles played by heme oxygenase-2 against transhemispheric diaschisis2019

    • Author(s)
      後藤 信一, 久保 亜希子, 森川 隆之, 梶村 眞弓, 末松 誠
    • Organizer
      第44回日本微小循環学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Neuroprotective effects by hypothermia are mediated through a coordinated suppression of acetyl CoA contents leading to a decrease in acetylcholine contents in neonatal hypoxia-ischemia2017

    • Author(s)
      Kajimura M, Takenouchi T, Sugiura Y, Hishiki T, and Suematsu M
    • Organizer
      The XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新生児低酸素性虚血性脳症における低体温療法による神経保護作用の分子機構:代謝解剖学的アプローチを用いて2017

    • Author(s)
      梶村 眞弓
    • Organizer
      第21回酸素ダイナミクス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] RICE(Rapid Image Contrast Enhancement):A color-coded algorithm to spot spatio-quantitative metabolic difference between two groups using MALDI imaging mass spectrometry data2016

    • Author(s)
      後藤 信一, 久保亜紀子, 善岡尊文, 末松誠, 梶村 眞弓
    • Organizer
      第41回日本微小循環学会総会
    • Place of Presentation
      コクヨホール(東京都港区)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] 虚血脳エネルギー代償機転の分子機構の解明 -代謝解剖学的アプローチを用いて-2016

    • Author(s)
      梶村 眞弓
    • Organizer
      第16回抗加齢医学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-06-11
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] 実験医学増刊 レドックス疾患学2018

    • Author(s)
      4.末松 誠, 納谷昌之, 塩田芽実, 山添昇吾, 久保亜紀子, 菱木貴子, 梶村 眞弓, 加部泰明
    • Total Pages
      276
    • Publisher
      羊土社
    • ISBN
      9784758103695
    • Related Report
      2017 Research-status Report
  • [Remarks]

    • URL

      http://www.sci.keio.ac.jp/en/people/detail.php?eid=00181&katagaki=3&bunya2_color=6&status=1

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://www.sci.keio.ac.jp/member/detail.php?eid=00181&katagaki=3&status=1

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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