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Neuroprotective effects of ADAMTS13 against delayed brain ischemia after subarachnoid hemorrhage

Research Project

Project/Area Number 26462170
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionNara Medical University

Principal Investigator

Fujioka Masayuki  奈良県立医科大学, 医学部, 非常勤講師 (20254518)

Co-Investigator(Kenkyū-buntansha) 三島 健一  福岡大学, 薬学部, 教授 (00320309)
Co-Investigator(Renkei-kenkyūsha) TAOKA Toshiaki  名古屋大学, 医学部, 准教授 (30305734)
ABE Kohji  大阪大学, 医学部, 特任准教授 (80571207)
NAKASE Hiroyuki  奈良県立医科大学, 医学部, 教授 (10217739)
Research Collaborator MUROI Carl, Izumi  
FUJIMURA Yoshihiro  
TSUBOI Akio  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsADAMTS13 / クモ膜下出血 / 脳虚血 / 脳動脈瘤 / 血栓 / 炎症 / VWF / MRI / 遅発性脳虚血 / 動物モデル
Outline of Final Research Achievements

ADAMTS13 cleaves VWF and reduces its prothrombotic and proinflammatory functions. Thus, ADAMTS13 protects the brain against acute ischemia by ameliorating post-ischemic brain hypoperfusion and inflammation. We studied the effect of ADAMTS13 on delayed cerebral ischemia after aneurysmal SAH. We evaluated the mice SAH model with 7.0 Tesla MRI and histology. The effects of ADAMTS13 on delayed cerebral microthrombi, cerebral vasospasm, neuronal inflammation, and neuronal death in the cerebral cortex and hippocampus were analyzed over time after SAH by comparing the groups with and without ADAMTS13 administration. ADAMTS13 significantly reduced microthrombosis, neuroinflammation and degenerative neurons, and improved neurological performance in SAH models. Our study with ADAMTS13 knockout mice signified neuroprotective effects of ADAMTS13 in SAH models. ADAMTS13 could provide a novel therapeutic approach for delayed cerebral ischemia after SAH as well as for acute ischemic stroke.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 2015 2014

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results)

  • [Journal Article] Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice2018

    • Author(s)
      Takafumi Nakano, Chisa Nishigami, Keiichi Irie, Yutaka Shigemori, Kazunori Sano, Yuta Yamashita, Takayuki Myose, Koji Tominaga, Koichi Matsuo, Yoshihiko Nakamura, Hiroyasu Ishikura, Hidetoshi Kamimura, Takashi Egawa, Kenichi Mishima
    • Journal Title

      J Stroke Cerebrovasc Dis

      Volume: 27 Issue: 3 Pages: 758-763

    • DOI

      10.1016/j.jstrokecerebrovasdis.2017.10.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 三島 健一、中野貴文、入江 圭一、藤岡政行2018

    • Author(s)
      脳梗塞モデルマウスを用いた漢方製剤五苓散のaquaporin 4阻害作用による脳浮腫改善効果
    • Journal Title

      福岡大学産学官連携研究機関 加齢脳科学研究所 2017年度研究成果報告書

      Volume: -

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 脳梗塞モデルマウスに対する播種性血管内凝固症候群治療薬 トロンボモデュリン アルファの効果2017

    • Author(s)
      三島 健一、藤岡政行、仲村佳彦、中野貴文、入江 圭一
    • Journal Title

      福岡大学産学官連携研究機関 加齢脳科学研究所 2016年度研究成果報告書

      Volume: - Pages: 53-61

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Evaluation of a filament perforation model for mouse subarachnoid hemorrhage using 7.0 Tesla MRI2016

    • Author(s)
      Muroi C, Kashiwagi Y, Rokugawa T, Tonomura M, Obata A, Nevzati E, Tsuboi A, Okuchi K, Mishima K, Abe K, Fujioka M
    • Journal Title

      J Clin Neurosci.

      Volume: 28 Pages: 141-147

    • DOI

      10.1016/j.jocn.2015.10.045

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Recombinant human soluble thrombomodulin ameliorates cerebral ischemic injury through a high-mobility group box 1 inhibitory mechanism without hemorrhagic complications in mice.2016

    • Author(s)
      Nakamura Y, Nakano T, Irie K, Sano K, Tanaka J, Yamashita Y, Satho T, Matsuo K, Fujioka M, Ishikura H, Mishima K.
    • Journal Title

      J Neurol Sci.

      Volume: 362 Pages: 278-282

    • DOI

      10.1016/j.jns.2016.01.047

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Time Course of Diffusion Kurtosis in Cerebral Infarctions of Transient Middle Cerebral Artery Occlusion Rat Model.2016

    • Author(s)
      Taoka T, Fujioka M, Kashiwagi Y, Obata A, Rokugawa T, Hori M, Masutani Y, Aoki S, Naganawa S, Abe K.
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 25 Issue: 3 Pages: 610-617

    • DOI

      10.1016/j.jstrokecerebrovasdis.2015.11.028

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mouse model of subarachnoid hemorrhage: technical note on the filament perforation model.2015

    • Author(s)
      Muroi C, Fujioka M, Marbacher S, Fandino J, Keller E, Iwasaki K, Mishima K.
    • Journal Title

      Acta Neurochir Suppl. 2015;120:315-20.

      Volume: 120 Pages: 315-320

    • DOI

      10.1007/978-3-319-04981-6_54

    • ISBN
      9783319049809, 9783319049816
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Utility of High-b-Value Diffusion-Weighted Magnetic Resonance Imaging in Evaluating Reversible Medial Longitudinal Fasciculus Syndrome Caused by Acute Brainstem Ischemia.2015

    • Author(s)
      Miki Y, Fujioka M, Taoka T, Tanaka H, Chitoku S, Matsuyama T, Tanaka S.
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 24 Issue: 6 Pages: 157-159

    • DOI

      10.1016/j.jstrokecerebrovasdis.2015.03.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication2015

    • Author(s)
      Nakano T, Irie K, Hayakawa K, Sano K, Nakamura Y, Tanaka M, Yamashita Y, Satho T, Fujioka M, Muroi C, Matsuo K, Ishikura H, Futagami K, Mishima K.
    • Journal Title

      Brain Res.

      Volume: 1624 Pages: 330-335

    • DOI

      10.1016/j.brainres.2015.07.027

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Filament perforation model for mouse subarachnoid hemorrhage: Surgical-technical considerations2014

    • Author(s)
      Muroi C, Fujioka M, Okuchi K, Fandino J, Keller E, Sakamoto Y, Mishima K, Iwasaki K, Fujiwara M
    • Journal Title

      Br J Neurosurg

      Volume: 28 Issue: 6 Pages: 722-732

    • DOI

      10.3109/02688697.2014.918579

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage.2014

    • Author(s)
      Muroi C, Fujioka M, Mishima K, Irie K, Fujimura Y, Nakano T, Fandino J, Keller E, Iwasaki K, Fujiwara M.
    • Journal Title

      J Thromb Haemost.

      Volume: 12(4) Issue: 4 Pages: 505-514

    • DOI

      10.1111/jth.12511

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selective neuronal loss in ischemic stroke and cerebrovascular disease2014

    • Author(s)
      Baron JC, Yamauchi H, Fujioka M, Endres M
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 34 Issue: 1 Pages: 2-18

    • DOI

      10.1038/jcbfm.2013.188

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Magnet Resonance Imaging in Experimental Mouse Subarachnoid Hemorrhage2014

    • Author(s)
      Muroi C, Kashiwakgi Y, Rokugawa T, Yamada T, Obata A, Fujioka M, Abe K
    • Journal Title

      J Neurol Surg A Cent Eur Neurosurg

      Volume: 75 (S 02) Pages: 64-64

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] クモ膜下出血後の遅発性脳虚血におけるADAMTS13の病態生理学的意義とその治療応用についての検討2014

    • Author(s)
      藤岡政行
    • Journal Title

      冲中記念成人病研究所年報

      Volume: 40 Pages: 59-62

    • Related Report
      2014 Research-status Report
  • [Journal Article] 私の研究 -My Research- 第5回 ADAMTS132014

    • Author(s)
      藤岡政行、藤村吉博
    • Journal Title

      Angiology Frontier

      Volume: 13 Pages: 58-63

    • Related Report
      2014 Research-status Report
  • [Presentation] Neuroprotective Effects of ADAMTS13 against Delayed Brain Ischemia after Aneurysmal Subarachnoid Hemorrhage2017

    • Author(s)
      Fujioka M, Muroi C, Tsuboi A, Okuchi K, Nakase H, Abe K, Mishima K
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ADAMTS 13 - Microthrombosis in Subarachnoid Hemorrhage - an Update -2017

    • Author(s)
      Muroi C, Fujioka M, Abe K, Keller E, Fujimura Y, Mishima K
    • Organizer
      Vasospasm 2017. The 14th International Conference on Neurovascular Events after Subarachnoid Hemorrhage
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recombinant human soluble thrombomodulin ameliorates cerebral ischemic injury through a high-mobility group box 1 inhibitory mechanism without hemorrhagic complications in mice2017

    • Author(s)
      Yoshihiko Nakamura, Takafumi Nakano, Keiichi Irie, Kazunori Sano, Junichi Tanaka, Yuta Yamashita, Tomomitsu Satho, Koichi Matsuo, Masayuki Fujioka, Hiroyasu Ishikura, Kenichi Mishima
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of delayed treatment with ADAMTS13 on cerebral ischemic injury compared with tPAs2017

    • Author(s)
      Takafumi Nakano, Keiichi Irie, Yuta Yamashita, Takayuki Myose, Kazunori Sano, Yoshihiko Nakamura, Tomomitsu Satho, Mamiko Kai, Koji Tominaga, Hidetoshi Kamimura, Kenichi Mishima, Takashi Egawa
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳梗塞時における酸化 LDL 誘発性炎症反応に対する thrombospondin-1 の役割2017

    • Author(s)
      中野貴文、入江圭一、山下郁太、明瀬孝之、高瀬友美、佐藤朝光、松尾宏一、佐野和憲、本多健治、神村英利、三島健一
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 長時間脳虚血マウスに対する血栓溶解薬 t-PA と DIC 治療薬 thrombomodulin の有用性2017

    • Author(s)
      安村真子、中野貴文、仲村佳彦、入江圭一、山下郁太、明瀬孝之、佐藤朝光、三島健司、松尾宏一、佐野和憲、本多健治、石倉宏恭、三島健一
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] クモ膜下出血後の脳虚血に対するADAMTS13の神経保護効果2016

    • Author(s)
      藤岡 政行, 室井 カール, 坪井 昭夫, 奥地 一夫, 中瀬 裕之, 阿部 浩司, 三島 健一
    • Organizer
      第75回日本脳神経外科学会学術総会
    • Place of Presentation
      福岡国際会議場、 福岡
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳動脈瘤破裂クモ膜下出血後の脳虚血病態に対するADAMTS13の 脳保護機能.2015

    • Author(s)
      藤岡 政行, 室井 カール, 奥地 一夫, 中瀬 裕之, 阿部 浩司, 三島 健一.
    • Organizer
      第74回日本脳神経外科学会学術総会
    • Place of Presentation
      ロイトン札幌, 札幌
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Filament Perforation Model for Mouse Subarachnoid Hemorrhage: Evaluation by 7.0T MRI2015

    • Author(s)
      Carl Muroi, Yuto Kashiwagi, Takemi Rokugawa, Misato Tonomura, Atsushi Obata, Edin Nevzati, Akio Tsuboi, Kenichi Mishima, Kohji Abe, Masayuki Fujioka.
    • Organizer
      Vasospasm 2015. 13th International Conference on Neuromuscular Events after Subarachnoid Hemorrhage
    • Place of Presentation
      Karuizawa Prince Hotel West, Karuizawa
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳虚血およびクモ膜下出血後の遅発性脳虚血病態に対するADAMTS13の脳保護機能2015

    • Author(s)
      藤岡 政行, 室井 カール, 松山 武, 阿部浩司、三島 健一
    • Organizer
      第40回日本脳卒中学会総会
    • Place of Presentation
      リーガロイヤルホテル広島 広島
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 虚血‐再潅流およびクモ膜下出血後の脳虚血病態に対するADAMTS13の脳保護機能2014

    • Author(s)
      藤岡 政行, 室井 カール, 松山 武, 三島 健一
    • Organizer
      第73回日本脳神経外科学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪 東京
    • Year and Date
      2014-10-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Magnet Resonance Imaging in Experimental Mouse Subarachnoid Hemorrhage2014

    • Author(s)
      Muroi C, Kashiwakgi Y, Rokugawa T, Yamada T, Obata A, Fujioka M, Abe K
    • Organizer
      Joint Annual Meeting 2014: Swiss Society of Neurosurgery, Swiss Society of Clinical Neurophysiology, Swiss Society of Neuropediatrics
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2014-06-12 – 2014-06-13
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2019-03-29  

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