Analysis and manipulation of acellular barrier in human blood-nerve barrier

• Project/Area Number: 25293203
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yamaguchi University
• Principal Investigator: KANDA Takashi 山口大学, 医学(系)研究科(研究院), 教授 (40204797)
• Co-Investigator(Renkei-kenkyūsha): TERASAKI Tetsuya 東北大学, 大学院薬学研究科, 教授 (60155463)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 血液神経関門 / 内皮細胞 / ペリサイト / 基底膜 / ラミニン / 炎症性ニューロパチー / ラミニンアイソフォーム / 非細胞バリアー

Outline of Final Research Achievements

Major basement membrane proteins composing blood-nerve barrier (BNB) were fibronectin, collagen type IV and laminin alpha 5. Differed from those of blood-brain barrier (BBB), laminin alpha 4 was barely detected. The differences of cellular properties constituting BBB and BNB may be responsible for these variations. Our results suggested that in BNB, without glia limitans which functions as acellular barrier for T cell intrusion in the nervous system parenchyma in BBB, the first basement membrane wrapping endothelial cells and pericytes itself functions as “acellular barrier”.

Research Products

• [Journal Article] Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis. (2015)
  • Author(s): Nishihara H, Shimizu F, Sano Y, Takeshita Y, Maeda T, Abe M, Koga M, Kanda T.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0121488-e0121488
  • DOI: 10.1371/journal.pone.0121488
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Markedly Increased IP-10 Production by Blood-Brain Barrier in Neuromyelitis Optica. (2015)
  • Author(s): Shimizu F, Nishihara H, Sano Y, Takeshita Y, Takahashi S, Maeda T, Takahashi T, Abe M, Koga M, Kanda T.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0122000-e0122000
  • DOI: 10.1371/journal.pone.0122000
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sera from patients with multifocal motor neuropathy disrupt the blood-nerve barrier. (2014)
  • Author(s): Fumitaka Shimizu, Masatoshi Omoto, Yasuteru Sano, Naoko Matsui, Ai Miyashiro, Ayako Tasaki, Toshihiko Maeda, Michiaki Koga, Ryuji Kaji, Takashi Kanda
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 85 Issue: 5 Pages: 526-537
  • DOI: 10.1136/jnnp-2013-305668
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes. (2014)
  • Author(s): Shimizu F, Sawai S, Sano Y, Beppu M, Misawa S, Nishihara H, Koga M, Kuwabara S, Kanda T.
  • Journal Title: PLOS One Volume: 9 Issue: 8 Pages: e104205-e104205
  • DOI: 10.1371/journal.pone.0104205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy. (2014)
  • Author(s): T. Furukawa, Noriko Matsui, K. Fujita, Ai Miyashiro, H. Nodera, Y. Izumi, Fumitaka Shimizu, K. Miyamoto, Y. Takahashi, Takashi Kanda, Susumu Kusunoki, Ryuji Kaji
  • Journal Title: J Neurol Sci Volume: 346 Issue: 1-2 Pages: 75-79
  • DOI: 10.1016/j.jns.2014.07.059
  • Peer Reviewed / Open Access
• [Journal Article] 免疫性神経疾患の病態とBBBおよびBNB. (2013)
  • Author(s): 前田敏彦、神田 隆
  • Journal Title: 日本臨床 Volume: 71 Pages: 789-794
• [Presentation] 糖尿病性末梢神経障害のBNBを構成する非細胞性バリアーの組織学的検討 (2016)
  • Author(s): 尾本雅俊、神田 隆
  • 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
• [Presentation] パネルディスカッション：免疫介在性ニューロパチーにおけるblood-nerve barrierの変化 (2015)
  • Author(s): 神田 隆
  • Organizer: 第26回日本末梢神経学会学術集会
  • Place of Presentation: ホテルブエナビスタ（長野県松本市）
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] Symposium: Cellular properties of peicytes in human blood-brain barrier and blood-nerve barrier (2015)
  • Author(s): Takashi Kanda
  • Organizer: 第38回日本神経科学会
  • 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: 2015-07-28
  • Invited
• [Presentation] BNBを構成する非細胞性バリアーの組織学的検討 (2015)
  • Author(s): 尾本雅俊、神田 隆
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] Immune-mediated disruption of neuro-vascular units in neuroimmunological diseases (2014)
  • Author(s): Takashi Kanda
  • Organizer: 第37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）
  • Year and Date: 2014-09-13
  • Invited
• [Presentation] 血液神経関門の破綻と末梢神経障害 (2014)
  • Author(s): 神田 隆
  • Organizer: 第25回日本末梢神経学会
  • Place of Presentation: ホテルルビノ京都堀川(京都府、京都市）
  • Year and Date: 2014-08-29
  • Invited
• [Presentation] 特別シンポジウム「糖尿病神経障害の進化と展望」：ヒト糖尿病性末梢神経障害の病理と血液神経関門の意義 (2013)
  • Author(s): 神田隆
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本(熊本県）
  • Invited
• [Presentation] The effect of sera from multifocal motor neuropathy on blood-nerve barrier. (2013)
  • Author(s): Fumitaka Shimizu, Yasuteru Sano, Naoko Mastui, Ai Miyashiro, Ryuji Kaji, Takashi Kanda.
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego Convention Center （USA)
• [Presentation] Novel human immortalized cell lines for the BBB/BNB research. (2013)
  • Author(s): Yasuteru Sano, Masaaki Abe, Fumitaka Shimizu, Toshihiko Maeda, Yoko Kashiwamura, Masatoshi Omoto, Motoharu Kawai, and Takashi Kanda.
  • Organizer: 25回日本神経免疫学会学術集会
  • Place of Presentation: 下関海峡メッセ(山口県）
  • Invited
• [Presentation] 血液神経関門の破綻が慢性炎症性脱髄性多発根ニューロパチーの臨床病型を決定する. (2013)
  • Author(s): 清水文崇，澤井 摂，佐野泰照，別府美奈子，三澤園子，前田敏彦，古賀道明，桑原 聡，神田 隆.
  • Organizer: 第24回日本末梢神経学会学術集会
  • Place of Presentation: 新潟朱鷺メッセ(新潟県）
• [Presentation] 血液神経関門の破綻が慢性炎症性脱髄性多発根ニューロパチーの臨床病型を決定する. (2013)
  • Author(s): 清水文崇，澤井 摂，佐野泰照，別府美奈子，三澤園子，前田敏彦，古賀道明，桑原 聡，神田 隆.
  • Organizer: 25回日本神経免疫学会学術集会
  • Place of Presentation: 下関海峡メッセ(山口県）