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Comprehensive analysis of neuronal regeneration, inflammation and gene therapy for post-ischemic insult by using experimental stroke models

Research Project

Project/Area Number 20249063
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

SAITO Nobuhito  東京大学, 医学部附属病院, 教授 (60262002)

Co-Investigator(Kenkyū-buntansha) IMAI Hideaki  東京大学, 医学部附属病院, 特任講師 (70359587)
Research Collaborator MIYAWAKI Satoru  東京大学, 大学院生
ONO Hideaki  東京大学, 大学院生
Project Period (FY) 2008 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥48,100,000 (Direct Cost: ¥37,000,000、Indirect Cost: ¥11,100,000)
Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2010: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2009: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2008: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Keywords脳虚血 / 神経再生 / 炎症 / プロテオミクス / 幹細胞 / 虚血耐性 / 低酸素負荷
Research Abstract

By applying variety of experimental stroke models for the basic research, we have exerted the comprehensive analysis of neuronal regeneration, inflammation and ischemic tolerance after ischemic insult. For the possibility of axonal regeneration treated by the cell transplantion, the small number of the transplanted cells remain in the lesion, appearing just homing, neither proliferation nor rewiring. In terms of the immunoreactions to ischemic insult of the brain, Cyclophilin C-associated protein(CyCAP), via stimulating calcineurin phosphatase activity, plays a pivotal role for activation of macrophage. The phenomenon of ischemic tolerance may link hypoxic preconditioning with vascular remodeling.

Report

(6 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008

All Journal Article (25 results) (of which Peer Reviewed: 20 results) Presentation (11 results)

  • [Journal Article] 局所脳虚血モデルにおけるMKP-1 mRNAの特異的かつ急峻な発現誘導2011

    • Author(s)
      堀川弘吏, 今井英明, 陳毅力, 宮脇哲, 越智崇, 伊藤明博, 中冨浩文, 斉藤延人
    • Journal Title

      脳循環代謝

      Volume: 23 Pages: 147-147

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sprague-Dawley(SD)ラット全脳虚血モデルの確立と応用(質量顕微鏡法による遅発性神経細胞死の網羅的解析)2011

    • Author(s)
      宮脇哲, 早坂孝宏, 今井英明, 堀川弘吏, 越智崇, 伊藤明博, 中冨浩文, 瀬藤光利, 斉藤延人
    • Journal Title

      脳循環代謝

      Volume: 23 Pages: 169-169

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Does hypoxic preconditioning induces angiogenesis and protects against focal cerebral ischemic damage in rats2011

    • Author(s)
      Kaie Kagoshima, Hideaki Imai, Chisato Kubota, Sandra Puentes, Masashi Kurachi, Yasuki Ishizaki, Yuhei Yoshimoto and Nobuhito Saito
    • Journal Title

      Kitakanto Med J

      Volume: 61 Pages: 1-8

    • NAID

      130000677711

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insights on the revascularization mechanism for treatment of Moyamoya disease based on the histopathologic concept of angiogenesis and arteriogenesis2011

    • Author(s)
      Saito N, Imai H.
    • Journal Title

      World Neurosurg

      Volume: 75 Issue: 2 Pages: 5-204

    • DOI

      10.1016/j.wneu.2010.10.004

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages2011

    • Author(s)
      Yamaguchi R, Hosaka M, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T.
    • Journal Title

      Brain Res

      Volume: 23 Pages: 55-65

    • DOI

      10.1016/j.brainres.2011.03.036

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sprague-Dawley (SD)ラット全脳虚血モデルの確立と応用(質量顕微鏡法による遅発性神経細胞死の網羅的解析)2011

    • Author(s)
      宮脇哲, 早坂孝宏, 今井英明, 堀川弘吏, 越智崇, 伊藤明博, 中冨浩文, 瀬藤光利, 斉藤延人
    • Journal Title

      脳循環代謝

      Volume: 23 Pages: 169-169

    • Related Report
      2011 Annual Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Does Hypoxic Preconditioning Induce Angiogenesis and Protect against Focal Cerebral Ischemic Damage in Rats?2011

    • Author(s)
      K Kagoshima, H Imai, C Kubota, S Puentes, M, Kurachi, Y Ishizaki, Y Yoshimoto, N Saito
    • Journal Title

      Kitakanto Med J

      Volume: 61 Pages: 1-8

    • NAID

      130000677711

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages2011

    • Author(s)
      Yamaguchi R, Hosaka M, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T
    • Journal Title

      Brain Res.

      Volume: 23 Pages: 55-65

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors2010

    • Author(s)
      Yoshikawa G, Momiyama T, Oya S, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
    • Journal Title

      J Neurosurg

      Volume: 113(4) Issue: 4 Pages: 835-850

    • DOI

      10.3171/2010.2.jns09989

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative toxicity2010

    • Author(s)
      Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T
    • Journal Title

      J Biol Chem

      Volume: 285 Issue: 1 Pages: 667-674

    • DOI

      10.1074/jbc.m109.053058

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors.2010

    • Author(s)
      Yoshikawa G, Momiyama T, Oya S, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
    • Journal Title

      J Neurosurg. 113(4)

      Pages: 835-850

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] The insight of revascularization mechanism based on angiogenesis and arteriogenesis from the experimental and clinical works in moyamoya disease2009

    • Author(s)
      H. Imai, M. Nakamura, C. Kubota, S. Puentes, A. Faried, Y. Yoshimoto, N. Saito.
    • Journal Title

      J Cereb Blood Flow & Metab

      Volume: 29 Issue: 1_suppl Pages: S376-S380

    • DOI

      10.1038/jcbfm.2009.151

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel modified method and its confirmation of injection into CSF via the cerebellomedullary cistern in mice2009

    • Author(s)
      Y. Chen, A. Ito and N. Saito
    • Journal Title

      J Cereb Blood Flow & Metab

      Volume: 29 Issue: 1_suppl Pages: 226-226

    • DOI

      10.1038/jcbfm.2009.141

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Attenuation of Notch signaling promotes the differentiation of neural progenitors into neurons in the hippocampal ca1 region after ischemic injury2009

    • Author(s)
      Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
    • Journal Title

      Neurosci

      Volume: 158 Issue: 2 Pages: 683-692

    • DOI

      10.1016/j.neuroscience.2008.10.043

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimental investigation of encephalo-myo-synangiosis using gyrencepharic brain of the miniature pig : histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis2009

    • Author(s)
      Nakamura M, Imai H, konno K, Kubota C, Seki K, Puentes S, Faired A, Yokoo H, Hata H, Yohimoto Y, Saito N.
    • Journal Title

      J Neurosurg Pediatr

      Volume: 3(6) Issue: 6 Pages: 488-495

    • DOI

      10.3171/2008.6.peds0834

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimental investigation of encephalo-myo-synangiosis using gyrencepharic brain of the miniature pig : histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis.2009

    • Author(s)
      Nakamura M, Imai H, konno K, Kubota C, Seki K, Puentes S, Faired A, Yokoo H, Hata H, Yohimoto Y, Saito N.
    • Journal Title

      J Neurosurg Pediatr 3(6)

      Pages: 488-495

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Attenuation of Notch signaling promotes the differentiation of neural progenitors into neurons in the hippocampal cal region after ischemic injury.2009

    • Author(s)
      Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
    • Journal Title

      Neurosci. 158

      Pages: 683-692

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative toxicity.2009

    • Author(s)
      Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T.
    • Journal Title

      J Biol Chem. 285

      Pages: 667-674

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Experimental investigation of encephalo-myo-synangiosis using gyrencepharic brain of the miniature pig : histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis2009

    • Author(s)
      Nakamura M, Imai H, Konno K, Kubota C, Seki K, Puentes S, Faired A, Yokoo H, Hata H, Yohimoto Y, Saito N
    • Journal Title

      J Neurosurg Pediatr 3

      Pages: 488-495

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive reactive oxygen species generation from autophagosome/lyso some in neuronal oxidative toxicity.2009

    • Author(s)
      Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T
    • Journal Title

      J Biol Chem 285

      Pages: 667-674

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia.2008

    • Author(s)
      Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
    • Journal Title

      Neuroreport

      Volume: 19(8) Pages: 805-809

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blocking pterygopalatine arterial blood flow decreases infarct volume variability in a mouse model of intraluminal suture middle cerebral artery occlusion2008

    • Author(s)
      Chen Y, Ito A, Takai K, Saito N.
    • Journal Title

      J Neurosci Methods

      Volume: 174 Issue: 1 Pages: 18

    • DOI

      10.1016/j.jneumeth.2008.06.021

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimental Model of Lacunar Infarction in the Gyrencephalic Brain of the Miniature Pig : Neurological Assessment and Histological, Immunohistochemical, and Physiological Evaluation of Dynamic Corticospinal Tract Deformation2008

    • Author(s)
      Tanaka Y, Imai H, Konno K, Miyagishima T, Kubota C, Puentes S, Aoki T, Hata H, Takata K, Yoshimoto Y, Saito N.
    • Journal Title

      Stroke

      Volume: 39 Issue: 1 Pages: 205-212

    • DOI

      10.1161/strokeaha.107.489906

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimental Model of Lacunar Infarction in the Gyrencephalic Brain of the Miniature Pig : Neurological Assessment and Histological, Immunohistochemical, and Physiological Evaluation of Dynamic Corticospinal Tract Deformation.2008

    • Author(s)
      Tanaka Y, Imai H, Konno K, Miyagishima T, Kubota C, Puentes S, Aoki T, Hata H, Takata K, Yoshimoto Y, Saito N.
    • Journal Title

      Stroke 39

      Pages: 205-212

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Blocking pterygopalatine arterial blood flow decreases infarct volume variability in a mouse model of intraluminal suture middle cerebral artery occlusion.2008

    • Author(s)
      Chen Y, Ito A, Takai K, Sai to N.
    • Journal Title

      J Neurosci Method 174

      Pages: 18-24

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] ラット中大脳動脈閉塞モデルにおけるMKP-1 mRNAの虚血側大脳半球での特異的かつ鋭敏な発現上昇2011

    • Author(s)
      堀川弘吏,今井英明,陳毅力,越智崇,伊藤明博,中冨浩文,齊藤延人
    • Organizer
      第12回日本分子脳神経外科学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-10-14
    • Related Report
      2011 Final Research Report
  • [Presentation] MKP-1 mRNA and protein expressions are induced in neuron at acute phase after focal cerebral ischemia2011

    • Author(s)
      H Horikawa, H Imai, Y Chen, T Ochi, A Ito, H Kanemitsu, H Nakatomi, N Saito
    • Organizer
      Brain 2011
    • Place of Presentation
      (ポスター)バルセロナ(スペイン)
    • Year and Date
      2011-05-27
    • Related Report
      2011 Final Research Report
  • [Presentation] MKP-1 mRNA and protein expression are induced in neuron at acute phase after focal cerebral ischemia2011

    • Author(s)
      H.Horikawa, H.Imai, Y.Chen, T.Ochi, A.Ito, H.Kanemitsu, H.Nakatomi, N.Saito
    • Organizer
      国際脳循環代謝学会
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2011-05-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Focal cerebral ischemia models of both lissencephalic and gyrencephalic species2011

    • Author(s)
      H. Imai, N. Saito
    • Organizer
      Brain 2011(教育コース)
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Final Research Report
  • [Presentation] FOCAL CEREBRAL ISCHEMIA MODELS OF BOTH LISSENCEPHALIC AND GYRENCEPHALIC SPECIES2011

    • Author(s)
      H.Imai, N.Saito
    • Organizer
      Brain 2011
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2011-05-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経細胞におけるフリーラジカルの産生機序と虚血細胞障害の解明(シンポジウム)2010

    • Author(s)
      今井英明、久保田知里、富沢真一郎、越智崇、伊藤明博、中冨浩文、斉藤延人
    • Organizer
      第11回日本分子脳神経外科学会
    • Place of Presentation
      仙台
    • Year and Date
      2010-08-27
    • Related Report
      2011 Final Research Report
  • [Presentation]2010

    • Author(s)
      今井英明、久保田知里、富沢真一郎、越智崇、伊藤明博、中冨浩文、斉藤延人
    • Organizer
      神経細胞におけるフリーラジカルの産生機序と虚血細胞障害の解明(シンポジウム)第11回日本分子脳神経外科学会
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] The insight of revascularization mechanism based on angiogenesis and arteriogenesis from the experimental and clinical works in moyamoya disease.2009

    • Author(s)
      H.Imai, M.Nakamura, C.Kubota, S.Puentes, A.Faried, Y.Yoshimoto, N.Saito
    • Organizer
      J Cereb Blood Flow Metab 29,S376-S380 (Abstract 364)
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] A novel modified method and its confirmation of injection into CSF via the cerebellomedullary cistern in mice2009

    • Author(s)
      Y.Chen, A.Ito, N.Saito
    • Organizer
      Journal of Cerebral Blood Flow & Metabolism 29,S213-S257 (Abstract 426)
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] 脳虚血耐性におけるプロテオミクス解析2009

    • Author(s)
      伊藤明博, 北芳博, 陳毅力, 徳岡涼美, 斉藤延人, 清水孝雄.
    • Organizer
      日本生化学会大会プログラム・講演要旨集82回Page4P-595
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] もやもや病に対する広範囲血行再建術後の血行再建パターンの解析2008

    • Author(s)
      今井英明, 中村光伸, 鹿児島海衛, 嶋口英俊, 風間健, 齊藤延人, 好本裕平
    • Organizer
      血管新生機序から考察したEMSの重要性日本脳神経外科学会総会CD-ROM抄録集(1347-9040)67回Page3J-04-P80-06
    • Related Report
      2010 Self-evaluation Report

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Published: 2008-04-01   Modified: 2016-04-21  

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