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Investigation into the mechanism of the blood-nerve barrier disruption in chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy

Research Project

Project/Area Number 24790886
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionYamaguchi University

Principal Investigator

SHIMIZU Fumitaka  山口大学, 医学(系)研究科(研究院), 助教 (90535254)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords自己免疫性ニューロパチー / 血液神経関門 / 慢性炎症性脱髄性根ニューロパチー / 多巣性運動ニューロパチー / 自己免疫性末梢神経疾患 / 末梢神経障害 / 国際情報交換 / 多国籍
Outline of Final Research Achievements

<Purpose> The aim of this project was to elucidate the severity and mechanism of breakdown of the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). <Methods> We evaluated the effects of sera obtained from patients with typical CIDP/atypical CIDP/MMN and control subjects on the expression of claudin-5 and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs). <Result> Sera obtained from the patients with typical CIDP/atypical CIDP/MMN decreased the amount of claudin-5 protein levels and TEER values in PnMECs. The autocrine secretion of VEGF in PnMECs induced by MMN sera and immunoglobulin G purified from MMN sera decreased the expression of claudin-5. <Conclusion> Sera from CIDP/MMN patients disrupt the BNB function. In MMN, the autocrine secretion of VEGF in PnMECs and autoantibodies against PnMECs may be responsible for the BNB disruption.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (26 results)

All 2015 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 6 results) Presentation (11 results) Book (2 results)

  • [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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / 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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sera from remitting and secondary progressive multiple sclerosis patients disrupt the blood-brain barrier.2014

    • Author(s)
      Shimizu F, Tasaki A, Sano Y, Ju M, Nishihara H, Oishi M, Koga M, Kawai M, Kanda T.
    • Journal Title

      PLOS One

      Volume: 9 Issue: 3 Pages: e92872-e92872

    • DOI

      10.1371/journal.pone.0092872

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Breakdown of the blood-brain barrier in neuromyelitis optica: Roles of matrix-metalloproteinases-2/9, vascular endothelial growth factor and autoantibodies against the blood-brain barrier.2014

    • Author(s)
      Shimizu F, Tasaki A, Kanda T.
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: 5 Pages: 2-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Autocrine MMP-2/9 secretion increases the BBB permeability in neuromyelitis optica.2014

    • Author(s)
      Tasaki A, Shimizu F, Sano Y, Fujisawa M, Takahashi T, Haruki H, Abe M, Koga M, Kanda T.
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 85 Issue: 4 Pages: 419-430

    • DOI

      10.1136/jnnp-2013-305907

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 血液神経関門と自己免疫性ニューロパチー2014

    • Author(s)
      清水文崇,神田 隆
    • Journal Title

      Peripheral Nerve

      Volume: 24 Pages: 54-62

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sera from patients with multifocal motor neuropathy disrupt the blood-nerve barrier.2013

    • Author(s)
      Shimizu F, Omoto M, Sano Y, Mastui N, Miyashiro A, Tasaki A, Maeda T, Koga M, Kaji R, Kanda T.
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 7 Issue: 5 Pages: 526-537

    • DOI

      10.1136/jnnp-2013-305405

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advanced glycation end-products disrupt the blood-brain barrier by stimulating the release of transforming growth factor-β by pericytes and vascular endothelial growth factor and matrix metalloproteinase-2 by endothelial cells in vitro.2013

    • Author(s)
      Fumitaka Shimizu
    • Journal Title

      Neurobiol Aging

      Volume: 34 Issue: 7 Pages: 1902-1912

    • DOI

      10.1016/j.neurobiolaging.2013.01.012

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blood-brain barrier destruction determines Fischer/Bickerstaff clinical phenotypes: an in vitro study2013

    • Author(s)
      Kazuyuki Saito, Fumitaka Shimizu, Michiaki Koga, Yasuteru Sano, Ayako Tasaki, Masa-aki Abe, Hiroyo Haruki, Toshihiko Maeda, S. Suzuki, Susumu Kusunoki, Hidehiro Mizusawa, Takashi Kanda.
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 84 Issue: 7 Pages: 756-765

    • DOI

      10.1136/jnnp-2012-304306

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 血液脳関門と神経免疫疾患2013

    • Author(s)
      清水文崇,神田 隆
    • Journal Title

      Brain and Nerve

      Volume: 65 Pages: 165-176

    • Related Report
      2013 Research-status Report
  • [Journal Article] Sera from neuromyelitis optica patients disrupt the blood-brain barrier2012

    • Author(s)
      Shimizu F, Sano Y, Takahashi T, Haruki H, Saito K, Koga M, Kanda T
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 83 Issue: 3 Pages: 288-297

    • DOI

      10.1136/jnnp-2011-300434

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pericyte-derived glial cell line-derived neurotrophic factor increase the expression of claudin-5 in the blood-brain barrier and the blood-nerve barrier2012

    • Author(s)
      Shimizu F, Sano Y, Saito K, Abe MA, Maeda T, Haruki H, Kanda T
    • Journal Title

      Neurochem Res

      Volume: 37 Issue: 2 Pages: 401-409

    • DOI

      10.1007/s11064-011-0626-8

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 傍腫瘍性小脳変性症を合併したLambert-Eaton筋無力症候群では血液脳関門が破綻する.2014

    • Author(s)
      清水文崇, 本村政勝, 中田るか,白石 裕一,佐野泰照, 神田 隆.
    • Organizer
      第55回日本神経学会学術集会総会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2014-05-23 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多発性硬化症患者血清が血液脳関門に及ぼす影響の解析2013

    • Author(s)
      清水文崇,田崎彩子,佐野泰照,朱 美和,前田敏彦,大石真莉子,古賀道明,神田 隆.
    • Organizer
      第54回日本神経学会学術集会総会
    • Place of Presentation
      東京(東京国際フォーラム)
    • Related Report
      2013 Research-status Report
  • [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)
    • Related Report
      2013 Research-status Report
  • [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25回日本神経免疫学会学術集会.
    • Place of Presentation
      下関(海峡メッセ)
    • Related Report
      2013 Research-status Report
  • [Presentation] 傍腫瘍性小脳変性症を合併したLambert-Eaton筋無力症候群では血液脳関門が破綻する.2013

    • Author(s)
      清水文崇,本村政勝,中田るか,白石 裕一,佐野泰照,神田 隆
    • Organizer
      第25回日本神経免疫学会学術集会
    • Place of Presentation
      下関(海峡メッセ)
    • Related Report
      2013 Research-status Report
  • [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
    • Place of Presentation
      San Diego, U.S.A
    • Related Report
      2013 Research-status Report
  • [Presentation] Sera from remitting and secondary progressive multiple sclerosis patients disrupt the blood-brain barrier.2013

    • Author(s)
      Fumitaka Shimizu, Ayako Tasaki, Yasuteru Sano, Takashi Kanda.
    • Organizer
      PACTRIMS
    • Place of Presentation
      Kyot (ウェスティンホテル京都),
    • Related Report
      2013 Research-status Report
  • [Presentation] 多巣性運動ニューロパチー血清は血液神経関門を破綻させる.2012

    • Author(s)
      清水文崇,佐野泰照,斎藤和幸,安部真彰,前田敏彦,春木明代,松井尚子,宮城 愛,梶 龍兒, 神田 隆.
    • Organizer
      第53回日本神経学会学術集会総会.
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 多巣性運動ニューロパチー血清による血液神経関門破綻メカニズムの解析.2012

    • Author(s)
      清水文崇,佐野泰照,古賀道明,田崎彩子,安部真彰,前田敏彦,春木明代,松井尚子,宮城 愛,梶 龍兒,神田 隆.
    • Organizer
      第23回日本末梢神経学会学術集会.
    • Place of Presentation
      九州大学医学部百年講堂(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] 多巣性運動ニューロパチー血清による血液神経関門破綻メカニズムの解析.2012

    • Author(s)
      清水文崇,佐野泰照,古賀道明,田崎彩子,安部真彰,前田敏彦,春木明代,松井尚子,宮城 愛,梶 龍兒,神田 隆.
    • Organizer
      第24回日本神経免疫学会学術集会.
    • Place of Presentation
      軽井沢プリンスホテルウエスト(長野)
    • Related Report
      2012 Research-status Report
  • [Presentation] The effect of advanced glycation end-products on blood-brain barrier.2012

    • Author(s)
      Fumitaka Shimizu, Yasuteru Sano, Hiroyo Haruki, and Takashi Kanda.
    • Organizer
      Neuroscience 13 Oct 2012.
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Book] 日本臨床 多発性硬化症と視神経脊髄炎- 血液神経関門とその障害モデル-2014

    • Author(s)
      清水文崇,神田 隆.
    • Publisher
      日本臨床社
    • Related Report
      2014 Annual Research Report
  • [Book] The Blood-Brain Barrier in Neuroinflammation. In Suzumura A, Ikenaka K, editors. Neuron-Glia Interaction in Neuroinflammation.2013

    • Author(s)
      Shimizu F, Kanda T
    • Total Pages
      22
    • Publisher
      New York, NY: Springer Science+Business Media New York.
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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