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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Nagasaki 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
• Keywords: 中枢 / 末梢神経 / 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

Research Products

• [Journal Article] Cilostazol strengthens barrier integrity in brain endothelial cells (2013)
  • 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
• [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 models (2012)
  • 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
• [Journal Article] Patented in vitroblood-brain barrier models in CNS drug discovery (2011)
  • 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
• [Journal Article] Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells (2010)
  • 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
• [Journal Article] Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity (2010)
  • 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
• [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
• [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)
  • Year and Date: 20121108-09
• [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)
  • Year and Date: 20120903-04
• [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
• [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
  • Year and Date: 20100902-04
• [Presentation] Development of in vitro monkey BBB model (2010)
  • 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)
  • Year and Date: 20100316-18