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In vitro blood-brain barrier reconstruction model (BBB Kit) and their application to the functional analysis

Research Project

Project/Area Number 22590243
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNagasaki University

Principal Investigator

NIWA Masami  長崎大学, 大学院・医歯薬学総合研究科, 教授 (20136641)

Co-Investigator(Renkei-kenkyūsha) TANAKA Kunihiko  長崎大学, 大学院・医歯薬学総合研究科, 准教授 (80380955)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords中枢 / 末梢神経 / 血液脳関門 / サル血液脳関門 / 血液脳関門再構成モデル / サル脳毛細血管内皮細胞 / 脳ペリサイト / アストロサイト / 薬物脳内移行性 / タイトジャンクション / ラット血液脳関門
Research Abstract

The blood-brain barrier (BBB), a member of the neurovascular unit (NVU), functions in communication between brain capillary endothelial cells and other neighboring cells such as astrocytes and pericytes. Many drugs that are currently under development are intended to act centrally, but they do not cross the BBB. Furthermore, the crosstalk between the BBB and related cells contributing to the NVU remains to be elucidated. Based on our breakthrough in using rat primary brain capillary endothelial cells, pericytes and astrocytes to create a triple co-culture BBB model (BBB Kit), an in vitro models for screening the BBB penetration of drug candidates and research on BBB pathophysiology, we succeeded in modeling the monkey BBB with primary monkey brain capillary endothelial cells, rat pericytes and rat astrocytes. In addition, we constructed a porcine BBB model consisting of porcine brain capillary endothelial cells, rat pericytes, and rat astrocytes

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (25 results)

All 2013 2012 2011 2010 Other

All Journal Article (15 results) (of which Peer Reviewed: 8 results) Presentation (10 results) (of which Invited: 1 results)

  • [Journal Article] Cilostazol strengthens barrier integrity in brain endothelial cells2013

    • Author(s)
      Shoji Horai, Shinsuke Nakagawa, Kunihiko Tanaka, Yoichi Morofuji, Pierre-Olivier Couraud, Maria A. Deli, Hiroki Ozawa, Masami Niwa
    • Journal Title

      Cell Mol Neurobiol

      Volume: 33 Pages: 291-307

    • NAID

      120006986215

    • Related Report
      2012 Final Research Report
  • [Journal Article] Cilosatzol strengthens barrier integrity in brain endothelial cells2013

    • Author(s)
      Shoji Horai
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 33 Issue: 2 Pages: 291-307

    • DOI

      10.1007/s10571-012-9896-1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Initial contact of glioblastoma cells with existing normal brain endothelial cells strengthen the barrier function via fibroblast growth factor 2 secretion: A new in vitro blood-brain barrier model2013

    • Author(s)
      Keisuke Toyoda
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 33 Issue: 4 Pages: 489-501

    • DOI

      10.1007/s10571-013-9913-z

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of brain capillary endothelial cell-based and epithelial (MDCK-MDR1, Caco-2 and VB-Caco-2) cell-based surrogate blood-brain barrier penetration models2012

    • Author(s)
      Eva Hellinger, Szilvia Veszelka, Andrea Toth, Fruzsina Walter, Agnes Kittel, Monika Laura Bakk, Karoly Tihanyi, Viktor Hada, Shinsuke Nakagawa, Thuy Dinh Ha Duy, Masami Niwa, Maria A Deli, Monika Vastag.
    • Journal Title

      Eurpean Jounal of Pharmaceutics and Biopharmaceutocs

      Volume: 82 Pages: 34-350

    • Related Report
      2012 Final Research Report
  • [Journal Article] Comparison of brain capillary endothelial cell-based and epithelial (MDCK-MDR1,Caco-2 and VB-Caco-2) cell-based surrogate blood-brain barrier penetration models2012

    • Author(s)
      Eva Hellinger
    • Journal Title

      Eurpean Jounal of Pharmaceutics and Biopharmaceutocs

      Volume: 82 Issue: 2 Pages: 340-351

    • DOI

      10.1016/j.ejpb.2012.07.020

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Patented in vitroblood-brain barrier models in CNS drug discovery2011

    • Author(s)
      Andrea Toth, Szilvia Veszelka, Shinsuke Nakagawa, Masami Niwa,Maria A. Deli
    • Journal Title

      Recent Patents on CNS Drug Discovery

      Volume: 6 Pages: 107-118

    • Related Report
      2012 Final Research Report
  • [Journal Article] Patented in vitro blood-brain barrier models in CNS drug discovery2011

    • Author(s)
      Andrea Toth
    • Journal Title

      Recent Patents on CNS Drug Discovery

      Volume: 6 Issue: 2 Pages: 107-118

    • DOI

      10.2174/157488911795933910

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient expression of iron transport proteins in the capillary of the developing rat brain2011

    • Author(s)
      W.M.Yang
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 31 Issue: 1 Pages: 93-99

    • DOI

      10.1007/s10571-010-9558-0

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lercanidipine rescues hippocampus pyramidal neurons from mild ischemia-induced delayed neuronal death in SHRSP2011

    • Author(s)
      Yasuko Sakura-Yamashita
    • Journal Title

      Celluar and Molecular Neurobiology

      Volume: 31 Issue: 4 Pages: 561-567

    • DOI

      10.1007/s10571-011-9649-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells2010

    • Author(s)
      Yoichi Morofuji, Shinsuke Nakagawa, Gohei So, Takeshi Hiu, Shoji Horai, Kentaro Hayashi, Kunihiko Tanaka, Kazuhiko Suyama, Maria A. Deli, Isumi Nagata, Masami Niwa
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 30 Pages: 727-735

    • NAID

      120006984678

    • Related Report
      2012 Final Research Report
  • [Journal Article] Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity2010

    • Author(s)
      Maria A. Deli, Szilvia Veszelkaa, Boglarka Csiszara, Andrea Totha, Agnes Kittel, Maria Csetec, Aron Siposc, Aniko Szalaic, Livia Fulopd, Botond Penked, Csongor S. Abrahama, Masami Niwa.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 22 Pages: 777-794

    • Related Report
      2012 Final Research Report
  • [Journal Article] 血液脳関門再構成モデルと機能解明への活用2010

    • Author(s)
      中川慎介、田中邦彦、田川泰、丹羽正美
    • Journal Title

      分子脳血管病

      Volume: 9(3) Pages: 17-25

    • Related Report
      2012 Final Research Report
  • [Journal Article] Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells2010

    • Author(s)
      Yoichi Morofuji
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 30 Pages: 727-735

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protection of the blood-brain barrier by pentosan against amyloid-ss-induced toxicity2010

    • Author(s)
      Maria A.Deli
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 22 Pages: 777-794

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血液脳関門再構成モデルと機能解明への活用2010

    • Author(s)
      中川慎介
    • Journal Title

      分子脳血管病

      Volume: 9 Pages: 17-25

    • Related Report
      2010 Annual Research Report
  • [Presentation] In vitro 血液脳関門再構成モデル(BBBキット)を用いたBBB機能の解析2012

    • Author(s)
      中川慎介、丹羽正美
    • Organizer
      第5回Japanese Consortium for Age-related Neurodegenerative disorders(J-CAN 2012)
    • Place of Presentation
      八重洲ファーストフィナンシャルビル(東京都)
    • Year and Date
      2012-08-25
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門 In vitro 再構成モデル(BBB キット)2012

    • Author(s)
      中川慎介、MA. Deli、DHDThuy、相良真由美、田中邦彦、丹羽正美
    • Organizer
      第14回応用薬理シンポジウム
    • Place of Presentation
      ベルクラシック甲府(山梨県)
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門 In vitro 再構成モデル(BBB キット)と機能解明への活用.2012

    • Author(s)
      中川慎介、MA. Deli、DHD Thuy、相良真由美、田中邦彦、丹羽正美
    • Organizer
      第24回日本脳循環代謝学会総会
    • Place of Presentation
      リーガロイヤルホテル広島(広島県)
    • Related Report
      2012 Final Research Report
  • [Presentation] Cilostazol rescues age-related ischemic BBB damages2011

    • Author(s)
      Tomohiro Takeshita
    • Organizer
      13^<th> International Symposium Signal Transduction in the blood-brain and blood-tumor barrier
    • Place of Presentation
      イスタンブール(トルコ)
    • Year and Date
      2011-09-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] An in vitro monkey BBB model2010

    • Author(s)
      Sinsuke Nakagawa
    • Organizer
      13^<th> International Symposium Signal Transduction in the blood-brain and blood-tumor barrier
    • Place of Presentation
      チューリッヒ(スイス)
    • Year and Date
      2010-09-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Development of in vitro monkey BBB model2010

    • Author(s)
      S Nakagawa, MA Deli1, DHD THUY, M Sagara, N Yamada, K Tanaka, M Niwa.
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2012 Final Research Report
  • [Presentation] An In vitro monkey BBB model.2010

    • Author(s)
      SNakagawa, MA Deli1, DHD Thuy, M Sagara, N Yamada, G So, R Tatsumi, K Tanaka, M Niwa
    • Organizer
      13th International Symposium on "Signalling at the Blood-Brain and Blood-Tumour Barriers
    • Place of Presentation
      Zurich
    • Related Report
      2012 Final Research Report
  • [Presentation] In vitro 血液脳関門再構成モデル(BBBキット)を用いたBBB機能の解析

    • Author(s)
      中川慎介
    • Organizer
      第5回Japanese Consortium for Age-related Neurodegenerative disorders(J-CAN 2012)
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 血液脳関門 In vitro 再構成モデル(BBB キット)

    • Author(s)
      中川慎介
    • Organizer
      第14回応用薬理シンポジウム
    • Place of Presentation
      甲府
    • Related Report
      2012 Annual Research Report
  • [Presentation] 血液脳関門 In vitro 再構成モデル(BBB キット)と機能解明への活用

    • Author(s)
      中川慎介
    • Organizer
      第24回日本脳循環代謝学会総会
    • Place of Presentation
      広島
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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