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A role of microglia in neurovascular coupling during cerebal ischemia

Research Project

Project/Area Number 15K06760
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionKeio University

Principal Investigator

Tomita Yutaka  慶應義塾大学, 医学部(信濃町), 講師(非常勤) (60276251)

Research Collaborator SUZUKI Norihiro  
KANNO Iwao  
UNEKAWA Miyuki  
MASAMOTO Kazuto  
YUKI Hiroya  
SOGA Naoto  
WATANABE Tatsushi  
HATAKEYAMA Nao  
Project Period (FY) 2015-10-21 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsマイクログリア / neurovascular unit / 脳梗塞 / 二光子顕微鏡 / 微小循環 / 低酸素負荷 / 血管新生
Outline of Final Research Achievements

In genetically-modified mice (CX3CR1-GFP mice)expressing the cortical microglia with green fluorescence protein (GFP), microglia and cortical microvessels were imaged through a closed-cranial window by using a Tomita-Seylaz method with two-photon laser scanning fluorescence microscopy repeatedly up to 3 weeks. There were no detectable differences in the soma area, number density, and number of processes of the GFP-positive microglia, whereas migrated and newborn microglia could be detected. Furthermore, appearance and/or migration of microglia adjacent to neovascular capillary under chronic hypoxia (8% oxygen) was exhibited.
A stimulation with a blue light in mice genetically expressing a light-sensitive cation channel, channelrhodopsin-2 in cortical astrocytes or neurons elicited intensity-dependent increase of cerebral blood flow. Pharmacological study exhibited independent mechanism of CBF control.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (41 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 2 results,  Open Access: 4 results) Presentation (32 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] Enhanced susceptibility to cortical spreading depression in two types of Na+, K+-ATPase α2 subunit-deficient mice as a model of familial hemiplegic migraine 2.2018

    • Author(s)
      Unekawa, M. Ikeda, K., Tomita, Y., Kawakami, K. and Suzuki, N.
    • Journal Title

      Cephalalgia

      Volume: 38 Issue: 9 Pages: 1515-1524

    • DOI

      10.1177/0333102417738249

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tomita-Seylaz法による慢性頭窓作製後のマウス大脳皮質ミクログリアの長期反復in vivoリアルタイム解析2017

    • Author(s)
      結城浩弥, 正本和人, 畝川美悠紀, 冨田裕, 菅野巖, 鈴木則宏.
    • Journal Title

      脳循環代謝

      Volume: 28 Pages: 249-256

    • NAID

      130006008228

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic diameter response of intraparenchymal penetrating arteries during cortical spreading depression and elimination of vasoreactivity to hypercapnia in anesthetized mice.2017

    • Author(s)
      Unekawa M, Tomita Y, Masamoto K, Toriumi H, Osada T, Kanno I, Suzuki N
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 37 Issue: 2 Pages: 657-670

    • DOI

      10.1177/0271678x16636396

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Establishment and evaluation of a new highly metastatic tumor cell line 5a-D-Luc-ZsGreen expressing both luciferase and green fluorescent protein2016

    • Author(s)
      Sudo H, Tsuji A B, Sugyo A, Takuwa H, Masamoto K, Tomita Y, Suzuki N, Imamura T, Koizumi M, Saga T
    • Journal Title

      Int. J. Oncol.

      Volume: 48 Issue: 2 Pages: 525-532

    • DOI

      10.3892/ijo.2015.3300

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model.2016

    • Author(s)
      Nishino A, Tajima Y, Takuwa H, Masamoto K, Taniguchi J, Wakizaka H, Kokuryo D, Urushihata T, Aoki I, Kanno I, Tomita Y, Suzuki N, Ikoma Y, Ito H.
    • Journal Title

      Scientific reports

      Volume: 27 Issue: 1 Pages: 25072-25072

    • DOI

      10.1038/srep25072

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dynamic flow velocity mapping from fluorescent dye transit times in the brain surface microcirculation of anesthetized rats and mice.2016

    • Author(s)
      Hoshikawa R, Kawaguchi H, Takuwa H, Ikoma Y, Tomita Y, Unekawa M, Suzuki N, Kanno I, Masamoto K.
    • Journal Title

      Microcirculation

      Volume: 26 Issue: 6 Pages: 416-425

    • DOI

      10.1111/micc.12285

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] アストロサイトによる脳血流調節2016

    • Author(s)
      正本和人, 畝川美悠紀, 冨田裕, 菅野巌, 鈴木則宏
    • Journal Title

      分子精神医学

      Volume: 16 Pages: 17-24

    • Related Report
      2015 Research-status Report
  • [Journal Article] Unveiling astrocytic control of cerebral blood flow with optogenetics2015

    • Author(s)
      Masamoto K, Unekawa M, Watanabe T, Toriumi H, Takuwa H, Kawaguchi H, Kanno I, Matsui K, Tanaka K F, Tomita Y, Suzuki N
    • Journal Title

      Scientific reports

      Volume: 5 Issue: 1 Pages: 11455-11455

    • DOI

      10.1038/srep11455

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperperfusion counteracted by transient rapid vasoconstriction followed by long-lasting oligemia induced by cortical spreading depression in anesthetized mice.2015

    • Author(s)
      Unekawa M, Tomita Y, Toriumi H, Osada T, Masamoto K, Kawaguchi H, Itoh Y, Kanno I, Suzuki N.
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 35 Issue: 4 Pages: 689-698

    • DOI

      10.1038/jcbfm.2014.250

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 大脳皮質拡延性抑制/脱分極が結ぶ片頭痛と脳卒中2018

    • Author(s)
      畝川美悠紀, 冨田裕, 鈴木則宏
    • Organizer
      第43回日本脳卒中学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Effect of spreading depolarization on cerebral blood flow and development of infarction under experimental ischemia in anesthetized mice.2017

    • Author(s)
      Unekawa M, Tomita Y, Toriumi H, Osada T, Masamoto K, Kanno I, Suzuki N
    • Organizer
      28th International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2017-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Repeated longitudinal in vivo imaging of cortical microglia under chronic hypoxia in the mice using twophoton microscopy with a closed cranial window technique.2017

    • Author(s)
      Kanno I, Masamoto K, Yuki H, Sugashi T, Unekawa M, Tomita Y, Suzuki N
    • Organizer
      28th International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2017-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spatiotemporal changes in cerebral blood flow induced by transcranial photostimulation to cortical neurons or astrocytes in the transgenic mice expressing channelrhodopsin-2.2017

    • Author(s)
      Hatakeyama N, Masamoto K, Unekawa M, Takuwa H, Kanno I, Matsui K, Tanaka KF, Tomita Y, Suzuki N
    • Organizer
      28th International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2017-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Longitudinal two-photon imaging of microvascular remodeling and microglial response to chronic hypoxia in in vivo mouse cortex2017

    • Author(s)
      Yuki T, Masamoto K, Unekawa M, Sugashi T, Tomita Y, Kanno I, Suzuki N
    • Organizer
      第42回日本微小循環学会総会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 慢性低灌流モデルマウスにおける安静時及び賦活時の脳神経機能評価2017

    • Author(s)
      漆畑拓弥, 田桑弘之, 高堂裕平, 正本和人, 菅野巖, 冨田裕, 鈴木則宏, 生駒洋子, 小畠隆行, 伊藤浩
    • Organizer
      第42回日本脳卒中学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 中大脳動脈閉塞時に発生する拡延性脱分極が脳血流と梗塞形成に及ぼす影響2017

    • Author(s)
      畝川美悠紀, 冨田裕, 鳥海春樹, 長田高志, 正本和人, 菅野巖, 鈴木則宏
    • Organizer
      第42回日本脳卒中学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経賦活とグリア賦活による脳血流反応の比較:オプトジェネティクスによる検討2017

    • Author(s)
      畠山菜緒, 正本和人, 畝川美悠紀, 田桑弘之, 菅野巖, 松井広, 田中謙二, 冨田裕, 鈴木則宏
    • Organizer
      第42回日本脳卒中学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳虚血後のグリア細胞の形状変化におけるin vivo長期解析2017

    • Author(s)
      渡部真子, 須貸拓馬, 蜂谷亮太, 安部貴人, 畝川美悠紀, 鳥海春樹, 冨田裕, 鈴木則宏, 田桑弘之, 菅野巖, 正本和人
    • Organizer
      日本機械学会 第30 回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低酸素誘発性脳微小血管リモデリングにおけるミクログリアの関与2017

    • Author(s)
      曽我直人, 結城浩弥, 須貸拓馬, 畝川美悠紀, 冨田裕, 菅野巖, 鈴木則宏, 正本和人
    • Organizer
      酸素ダイナミクス研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Na+,K+-ATPase a2サブユニット遺伝子欠損マウスにおける皮質拡延性抑制に対する感受性と脳内c-Fos発現分布2017

    • Author(s)
      畝川美悠紀, 池田啓子, 冨田裕, 川上潔, 鈴木則宏
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Widespread c-Fos expression after cortical spreading depression; possible differences between two types of animal models of familial hemiplegic migraine 2.2017

    • Author(s)
      Unekawa M., Ikeda K., Tomita Y., Kawakami K., Suzuki N.
    • Organizer
      The XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhanced susceptibility to cortical spreading depression and different degree in two-types of Na+,K+-ATPase a2 subunit-deficient mice as a model of familial hemiplegic migraine 2.2017

    • Author(s)
      Unekawa M., Ikeda K., Tomita Y., Kawakami K., Suzuki N.
    • Organizer
      18th Congress of the International Headache Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hemodynamic response to optogenetic activation of ChR2-expressing neurons or astrocytes in the mouse cortex.2017

    • Author(s)
      Hatakeyama N., Masamoto K., Unekawa M., Takuwa H., Kanno I., Matsui K., Tanaka K. F., Tomita Y., Suzuki N.
    • Organizer
      第9回光操作研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cerebral blood flow responses to photostimulation in the transgenic miceexpressing channelrhodopsin-2 in the cortical neurons or astrocytes.2017

    • Author(s)
      Hatakeyama N., Masamoto K., Unekawa M., Takuwa H., Kanno I., Matsui K., Tanaka K., Tomita Y., Suzuki N.
    • Organizer
      The XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tomita-Seylaz法による慢性頭窓作成後のマウス大脳皮質ミクログリアのin vivo長期反復解析2016

    • Author(s)
      結城浩弥, 正本和人, 畝川美悠紀, 冨田裕, 菅野巖, 鈴木則宏
    • Organizer
      第59回日本脳循環代謝学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 一時的脳虚血時に発生する拡延性脱分極に伴う血流変化と梗塞形成に対する影響2016

    • Author(s)
      畝川美悠紀, 冨田裕, 鳥海春樹, 長田高志, 正本和人, 菅野巖, 鈴木則宏
    • Organizer
      第59回日本脳循環代謝学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] オプトジェネティクスを用いたアストロサイト・ニューロン賦活による脳血流空間伝播の比較2016

    • Author(s)
      畠山菜緒, 正本和人, 畝川美悠紀, 田桑弘之, 菅野巖, 松井広, 田中謙二, 冨田裕, 鈴木則宏
    • Organizer
      第59回日本脳循環代謝学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 貧困灌流モデルマウスにおける神経細胞分布密度および脳血管・神経機能評価2016

    • Author(s)
      田桑弘之, 漆畑拓弥, 田島洋佑, 西野明日香, 正本和人, 菅野巖, 冨田裕, 鈴木則宏, 生駒洋子, 伊藤浩
    • Organizer
      第59回日本脳循環代謝学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Acceleration of red blood cells in intraparenchymal capillaries and dilation of arterial diameter in response to hypercapnia were diminished after passage of cortical spreading depression in anesthetized mice.2016

    • Author(s)
      Tomita Y, Unekawa M, Toriumi H, Osada T, Masamoto K, Kawaguchi H, Itoh Y, Kanno I, Suzuki N.
    • 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] Dynamic flow velocity mapping based on transient time measurements of fluorescent dye2016

    • Author(s)
      Hoshikawa R, Kawaguchi H, Takuwa H, Ikoma Y, Tomita Y, Unekawa M, Suzuki N, Kanno I, Masamoto K.
    • 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] Cerebral microvascular restructing and microglial adaptation to chronic hypoxia in the animal models.2016

    • Author(s)
      Masamoto K, Kanno I, Tomita Y, Suzuki N.
    • 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
    • Invited
  • [Presentation] In vivo imaging and quantification of glucose transfer using 2-NBDG in the mouse cortex with two-photon microscopy.2016

    • Author(s)
      Takeda H, Suzuki H, Murata R, Takuwa H, Kanno I, Tomita Y, Suzuki N, Yamada K, Masamoto K.
    • 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] Heterogeneous response of microcirculation to spreading depolarization evoked during middle cerebral artery occlusion in anesthetized mice.2016

    • Author(s)
      Unekawa M, Tomita Y, Toriumi H, Osada T, Masamoto K, Kanno I, Suzuki N.
    • 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] マウス大脳における神経細胞の空間分布と機能活動に関する定量解析2016

    • Author(s)
      武田寛史, 田桑弘之, 季斌, 佐原成彦, 冨田裕, 鈴木則宏, 菅野巖, 須原哲也, 樋口真人, 正本和人
    • Organizer
      第25回日本バイオイメージング学会学術集会
    • Place of Presentation
      名古屋市立大学薬学部 宮田専治記念ホール(愛知県名古屋市)
    • Year and Date
      2016-09-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Response of cerebral blood flow to optogenetic photostimulation of cortical neurons and astrocytes2016

    • Author(s)
      冨田裕, 渡部竜志, 正本和人, 畝川美悠紀, 鳥海春樹, 田桑弘之, 菅野巌, 松井広, 田中謙二, 鈴木則宏
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Response of cerebral blood flow to optogenetic photostimulation of cortical neurons and astrocytes2016

    • Author(s)
      冨田裕, 渡部竜志, 正本和人, 畝川美悠紀, 鳥海春樹, 田桑弘之, 菅野巌, 松井広, 田中謙二, 鈴木則宏
    • Organizer
      第57回日本神経学会学術大会(神戸)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 生体二光子顕微鏡法を用いたグリア脳血管の長期相互作用の解析2016

    • Author(s)
      新タ雅啓, 中原智美, 星川椋, 結城浩弥, 田桑弘之, 冨田裕, 鈴木則宏, 菅野巖, 正本和人
    • Organizer
      第25回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Research-status Report
  • [Presentation] オプトジェネティクスを用いた脳賦活による脳血流反応の空間伝播解析2015

    • Author(s)
      渡部竜志, 正本和人, 畝川美悠紀, 冨田裕, 田桑弘之, 菅野巖, 松井広, 田中謙二, 鈴木則宏
    • Organizer
      第4回ニューロフォトニクス研究会
    • Place of Presentation
      ホテルグランドヒル市ヶ谷(東京都新宿区)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 二光子顕微鏡を用いた生体マウス脳内ミクログリアの三次元長期イメージングと定量解析2015

    • Author(s)
      結城浩弥, 正本和人, 畝川美悠紀, 冨田裕, 鳥海春樹, 海老根妙子, 菅野巖, 鈴木則宏
    • Organizer
      第4回ニューロフォトニクス研究会
    • Place of Presentation
      ホテルグランドヒル市ヶ谷(東京都新宿区)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 家族性片麻痺性片頭痛2型モデルマウスにおける皮質拡延性抑制感受性および反応性2015

    • Author(s)
      畝川美悠紀, 池田啓子, 冨田裕, 鳥海春樹, 海老根妙子, 川上潔, 鈴木則宏
    • Organizer
      第43回日本頭痛学会総会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 大脳皮質性拡延性抑制が実質内穿通動脈口径と局所脳血流および二酸化炭素負荷に対する反応性に及ぼす影響2015

    • Author(s)
      畝川美悠紀, 冨田裕, 鳥海春樹, 長田高志, 正本和人, 菅野巖, 鈴木則宏
    • Organizer
      第27回日本脳循環代謝学会総会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report

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Published: 2015-10-21   Modified: 2019-03-29  

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