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Protective effect for antioxidative peptide against disruption of blood brain barrier induced ischemic injury

Research Project

Project/Area Number 24500423
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionJuntendo University

Principal Investigator

URABE Takao  順天堂大学, 医学部, 教授 (60291663)

Co-Investigator(Kenkyū-buntansha) SIMISAWA Tatsuo  東京大学, 医学部, 講師 (90231365)
Research Collaborator MIYAMOTO Nobukazu  
TANAKA Yasutaka  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアドレノメデュリン / 抗酸化ペプチド / 虚血性大脳白質障害 / 酸化ストレス / 高血糖 / 加齢 / 脳保護 / 認知障害 / 脳虚血 / 白質障害 / 血管内皮細胞 / 血液脳関門 / 細胞内シグナル伝達
Outline of Final Research Achievements

This study demonstrated that ischemic white matter injury was increased in adrenomedullin (AM) deficiency, which induced oxidative stress.
We indicated that adrenomedullin downregulation results in increase in oxidative stress after cerebral hypoperfusion in mice cerebral white matter. Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM deficiency group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM deficiency group.
White matter injury was more exacerbated because of hyperglycemia in aged AM deficiency group. The results indicated that adrenomedullin may be an important target in the control of ischemic white matter injury.

Report

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

Research Products

(29 results)

All 2014 2013 2012

All Journal Article (18 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results)

  • [Journal Article] Visceral fat accumulation is associated with cerebral small vessel disease.2014

    • Author(s)
      Kazuo Yamashiro, Ryota Tanaka, Yasutaka Tanaka, Nobukazu Miyamoto, Yoshiaki Shimada, Yuji Ueno, Takao Urabe, Nobutaka Hattori
    • Journal Title

      European Journal of Neurology

      Volume: 21 Pages: 667-673

    • DOI

      10.1111/ene.12374

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial cell proliferation in Swine experimental aneurysm after coil embolization.2014

    • Author(s)
      Yumiko Mitome-Mishima, Munetaka Yamamoto, Kenji Yatomi, Senshu Nonaka, Nobukazu Miyamoto, Takao Urabe, Hajime Arai, Hidenori Oishi
    • Journal Title

      PLoS One

      Volume: 9

    • DOI

      10.1371/journal.pone.0089047

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of durations of antiplatelet use and vascular risk factors with the presence of cerebral microbleeds.2014

    • Author(s)
      Kazuo Yamashiro, Ryota Tanaka, Yasuyuki Okuma, Yuji Ueno, Yasutaka Tanaka, Nobutaka Hattori, Takao Urabe
    • Journal Title

      Journal of stroke and cerebrovascular diseases

      Volume: 23 Pages: 433-440

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion in mice.2014

    • Author(s)
      Yumiko Mitome-Mishima, Nobukazu Miyamoto, Tanaka R, Shimosawa T, Oishi H, Arai H, Hattori N, Urabe T
    • Journal Title

      BioMedical Research International

      Volume: 2014 Pages: 861632-861632

    • DOI

      10.1155/2014/861632

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral ischemia in mice.2014

    • Author(s)
      Yoshiaki Shimada, Ryota Tanaka, Hideki Shimura, Kazuo Yamshiro, Takao Urabe, Nobutaka Hattori
    • Journal Title

      Neuroscience

      Volume: 278 Pages: 113-121

    • DOI

      10.1016/j.neuroscience.2014.07.073

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Differences in phosphodiesterase 3A and 3B expression after ischemic insult.2013

    • Author(s)
      Yumiko Mitome-Mishima, Nobukazu Miyamoto, Ryota Tanaka, Hidenori Oishi, Hajime Arai, Nobutaka Hattori, Takao Urabe
    • Journal Title

      Neuroscience Research

      Volume: 75 Pages: 340-348

    • DOI

      10.1016/j.neures.2013.02.006

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic brain ischemia induces the expression of glial glutamate transporter EAAT2 in subcortical white matter.2013

    • Author(s)
      Yuko Yatomi, Ryota Tanaka, Hideki Shimura, Nobukazu Miyamoto, Kazuo Yamashiro, Masashi Takanashi, Takao Urabe, Nobutaka Hattori
    • Journal Title

      Neuroscience

      Volume: 244 Pages: 113-121

    • DOI

      10.1016/j.neuroscience.2013.04.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.2013

    • Author(s)
      Shinichi Teramoto, Hideki Shimura, Ryota Tanaka, Yoshiaki Shimada, Nobukazu Miyamoto, Hajime Arai, Takao Urabe, Nobutaka Hattori
    • Journal Title

      PLoS One

      Volume: 8

    • DOI

      10.1371/journal.pone.0066001

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of diabetes and prediabetes on the short-term prognosis in patients with acute ischemic stroke.2013

    • Author(s)
      Ryota Tanaka, Yuji Ueno, Nobukazu Miyamoto, Kazuo Yamashiro, Yasutaka Tanaka, Hideki Shimura, Nobutaka Hattori, Takao Urabe
    • Journal Title

      Jornal of the Neurological Sciences

      Volume: 332 Pages: 45-50

    • DOI

      10.1016/j.jns.2013.06.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] インクレチンの脳梗塞領域縮小効果.2013

    • Author(s)
      卜部貴夫
    • Journal Title

      Diabetes Frontier

      Volume: 24 Pages: 286-290

    • Related Report
      2013 Research-status Report
  • [Journal Article] 脳白質障害後のオリゴデンドロサイトの再生メカニズム.2013

    • Author(s)
      宮元伸和,卜部貴夫
    • Journal Title

      実験医学

      Volume: 31 Pages: 2204-2209

    • Related Report
      2013 Research-status Report
  • [Journal Article] Benefits of prestroke use of angiotensin type 1 receptor blockers on ischemic stroke severity.2012

    • Author(s)
      NobukazuMiyamoto, Yasutaka Tanaka, Yuji Ueno , Ryota Tanaka , Nobutaka Hattori, Takao Urabe
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 21 Pages: 363-368

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Art and Parkinson's disease : a dramatic change in an artist's style as an initial symptom2012

    • Author(s)
      Shimura H, et al
    • Journal Title

      J Neurol.

      Volume: (In Press) Pages: 879-81

    • DOI

      10.1007/s00415-011-6271-y

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lamotrigineの神経保護作用2012

    • Author(s)
      卜部貴夫,北角和浩
    • Journal Title

      神経内科

      Volume: 76 Pages: 601-612

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 脳卒中急性期治療の実際;内科的治療(rt-PA, 薬物療法など).特集 徹底ガイド 脳卒中Q&A―プレホスピタルからリハビリまで―.2012

    • Author(s)
      卜部貴夫
    • Journal Title

      救急集中治療

      Volume: 24 Pages: 881-888

    • Related Report
      2012 Research-status Report
  • [Journal Article] ヘパリン;メインテーマ 心原性脳塞栓症と心房細動.2012

    • Author(s)
      卜部貴夫
    • Journal Title

      Clinical Neuroscience

      Volume: 30 Pages: 1266-1267

    • Related Report
      2012 Research-status Report
  • [Journal Article] 動脈硬化のハイリスクグループにおける脂質管理の意義と実際;脳梗塞の予防.テーマ 脂質異常症.2012

    • Author(s)
      上野祐司,卜部貴夫
    • Journal Title

      Medical Practice

      Volume: 29 Pages: 2081-2084

    • Related Report
      2012 Research-status Report
  • [Journal Article] 脳保護研究の現状と展望;虚血性白質障害の分子機構と新たな治療戦略,第53回日本神経学会学術大会 シンポジウム(1)-1-2.2012

    • Author(s)
      卜部貴夫
    • Journal Title

      臨床神経学

      Volume: 52 Pages: 908-910

    • Related Report
      2012 Research-status Report
  • [Presentation] 脳保護とNVU:虚血性脳損傷における細胞内保護シグナル伝達系の関わりとNVU protection.2014

    • Author(s)
      卜部貴夫
    • Organizer
      第26回日本脳循環代謝学会総会(シンポジウム)
    • Place of Presentation
      岡山(岡山コンベンションセンター)
    • Year and Date
      2014-11-21 – 2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 加齢による慢性脳虚血後白質損傷の差異,修復メカニズムについての検討.2014

    • Author(s)
      宮元伸和,荒井 健,早川和秀,Loc-Duyen D. Pham,松崎粛統,Ji Hae Seo,Eng H. Lo,田中亮太,卜部貴夫,服部信孝
    • Organizer
      第55回日本神経学会学術集会
    • Place of Presentation
      福岡(福岡国際会議場・福岡サンパレス・福岡国際センター)
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 虚血性脳損傷に対する細胞内シグナル伝達系制御による治療戦略.2013

    • Author(s)
      卜部貴夫
    • Organizer
      第38回日本脳卒中学会総会(シンポジウム)
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 虚血性白質障害の分子メカニズムと防御戦略.2013

    • Author(s)
      卜部貴夫
    • Organizer
      第38回日本脳卒中学会総会(イブニングセミナー)
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] アドレノメデュリンノックアウトマウスを用いた慢性脳低灌流モデルにおける虚血性白質障害の検討.2013

    • Author(s)
      19. 三島有美子,田中亮太,宮元伸和,大石英則,新井一,服部信孝,卜部貴夫
    • Organizer
      第38回日本脳卒中学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] db/db マウスにおける白質障害進展のメカニズムに関する検討.2013

    • Author(s)
      20. 矢富裕子,田中亮太,山城一雄,服部信孝,卜部貴夫
    • Organizer
      第38回日本脳卒中学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 強力スタチン治療と脳梗塞予防」急性期治療におけるスタチンの関与.2013

    • Author(s)
      卜部貴夫,上野祐司,渡邉雅男,宮元伸和
    • Organizer
      第16回日本栓子検出と治療学会(シンポジウム)
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] 「脳卒中発症予防のためのrisk管理~best medical treatmentを目指して~」;脳梗塞における糖尿病の関与.2012

    • Author(s)
      卜部貴夫
    • Organizer
      第37回日本脳卒中学会総会(シンポジウム)
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 脳卒中:脳保護研究の現状と展望(Neuroprotection-Update)」;虚血性白質障害の分子機構と新たな防御戦略.2012

    • Author(s)
      卜部貴夫
    • Organizer
      第53回日本神経学会学術大会(シンポジウム)
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 高齢者における抗血小板療法のリスクとベネフィット2012

    • Author(s)
      卜部貴夫
    • Organizer
      第54回日本老年医学会学術集会(ランチョンセミナー)
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 「脳血管障害と自律神経障害」;脳虚血の病態からみた治療2012

    • Author(s)
      卜部貴夫
    • Organizer
      第65回日本自律神経学会総会(教育セミナー)
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report

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

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