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Basic research for the comprehensive analysis of selective whitematter injury and the axonal regeneration

Research Project

Project/Area Number 22591577
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

IMAI Hideaki  東京大学, 医学部附属病院, 特任講師 (70359587)

Co-Investigator(Kenkyū-buntansha) SAITO Nobuhito  東京大学, 医学部附属病院, 教授 (60262002)
ISHIZAKI Yasuki  群馬大学, 大学院・医学系研究科, 教授 (90183003)
保坂 公平  群馬大学, 医学研究科, 教授 (70108992)
Co-Investigator(Renkei-kenkyūsha) SETOU Mitsutoshi  浜松医科大学, 医学部, 教授 (20302664)
Research Collaborator 堀川 弘吏  東京大学, 大学院生
宮脇 哲  東京大学, 大学院生
小野 秀明  東京大学, 大学院生
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脳梗塞 / 白質障害 / 病態解析 / 質量顕微鏡 / 軸索再生 / 細胞移植治療 / ラット白質梗塞モデル / 血管内皮細胞 / 虚血細胞死 / 細胞移植
Research Abstract

Sprague-Dawley rats were used. Under general anesthesia endothelin-1(ET-1:0.5μg/μl) was stereotactically injected into unilateral internal capsule to induce selective white matter damage.Selective white matter injury was evaluated by MRI, and particularly axonal injury was confirmed by specific APP immunoreactivity. The increased immunoreactivitiy for ED1 was observed in the lesion from3 days to 2 weeks after injection showing the activated microglia migrated and occupied the lesion of white matter injury. Imaging mass spectrometry (IMS) revealed the dynamicchange of phosphatidylcholines comprehensively IMS has tremendous potentials to provide the new insight in terms of the dynamic molecular changes invisible under conventional modality.The microvascular endothelial cells (MVECs) were prepared from rat cerebra for the cell transplantation. MVECs were transplanted into the ischemic lesion of internal capsule. MVECtransplantation improved the behavioral outcome and induced remyelion. Also the inflammatory response was repressed by MVEC transplantation. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter mayprovide important information for the development of effective therapies for white matter ischemia.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2013 2012 2011 2010 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (11 results)

  • [Journal Article] Symptomatic recurrence of intracranial arterial dissections: follow-up study of 143 consecutive cases and pathological investigation.2013

    • Author(s)
      H Ono, H Nakatomi, K Tsutsumi, T Inoue, A Teraoka, Y Yoshimoto, T Ide, C Kitanaka, K Ueki, H Imai, N Saito.
    • Journal Title

      Stroke

      Volume: 44(1) Issue: 1 Pages: 126-31

    • DOI

      10.1161/strokeaha.112.670745

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a Genetic Variant Common to Moyamoya Disease and Intracranial Major Artery Stenosis/Occlusion.2012

    • Author(s)
      S Miyawaki, H Imai, S Takayanagi, A Mukasa, N Hirofumi, N Saito.
    • Journal Title

      Stroke

      Volume: 43(12):3371-4 Issue: 12 Pages: 3371-3374

    • DOI

      10.1161/strokeaha.112.663864

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brain microvascular endothelial cell transplantation ameliorates ischemicwhite matter damage.2012

    • Author(s)
      Puentes S, Kurachi M, Shibasaki K, Naruse M, Yoshimoto Y, Mikuni M, Imai H, Ishizaki Y.
    • Journal Title

      Brain Res

      Volume: 1469 Pages: 43-53

    • DOI

      10.1016/j.brainres.2012.06.042

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ono Successful treatment of cerebral hemorrhage using computed tomography angiography in a patient with left-ventricular-assist device. M.2012

    • Author(s)
      Morito H, Nishimura T, Ando M, Kinoshita O, Hisagi M, Imai H, Iijima A, Motomura N, Kyo S
    • Journal Title

      J Artif Organs.

      Volume: 24巻1号

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 【イメージテクノロジーの進歩と脳卒中治療】手術支援としてのニューロイメージング高精細融合 3 次元画像を用いた脳血管障害手術シミュレーションの構築手法の工夫と手術戦略上の利点(原著論文/特集).2012

    • Author(s)
      宮脇 哲, 早坂 孝宏, 今井 英明, 小野秀明, 堀川 弘吏, 越智 崇, 伊藤 明博
    • Journal Title

      TheMt. Fuji Workshop on CVD (0289-8438)

      Volume: 30巻

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ラット選択的白質障害モデルに おけるストレス脆弱性の検討(会議録).2012

    • Author(s)
      小野秀明,今井英明,宮脇哲,堀川弘吏,越智崇,伊藤明博,宮田茂雄,倉知正,石崎泰樹,山形弘隆,三國雅彦,斉藤延人
    • Journal Title

      脳循環代謝(0915-9401)

      Volume: 24巻1号

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 脊髄に発生した glioneuronal tumor with neuropil-like islands の一例(会議録/症例報告)2012

    • Author(s)
      池村 雅子, 篠崎 綾, 今井 英明, 石井一彦, 齊藤 邦昭, 武笠 晃丈, 斉藤 延人,柴原 純二, 深山 正久.
    • Journal Title

      Brain Tumor Pathology(1433-7398)

      Volume: 29巻Suppl

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 村血ストレスに伴う海馬神経細胞の分子動態解析 質量顕微鏡法を用いた分子動態解析(会議録)2012

    • Author(s)
      阿部 浩幸, 池村 雅子, 花北 俊也, 今井 英明, 冨 浩文, 瀬藤 光利 , 斉藤 延人 虚 英明,五ノ井 渉, 萩原 良哉, 高澤 豊
    • Journal Title

      脳循環代謝(0915-9401)

      Volume: 24巻1号

    • Related Report
      2012 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
      2012 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
      2012 Final 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)(会議録)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(0915-9401)

      Volume: 23巻 1号

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 延人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(会議録)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(0915-9401)

      Volume: 23巻1号

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Does hypoxic preconditioning induce angiogenesis and protect against focal cerebral ischemic damage in Rats2011

    • 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
      2012 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

    • Related Report
      2011 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] 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 Pages: 204-205

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [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
      2010 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
      2010 Annual 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
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 虚血ストレス下における MKP-1 の発現上昇及び ERK の発現調節を介し たその役割(会議録)脳循環代謝2010

    • Author(s)
      堀川 弘吏, 今井 英明,村田 知里, 小野 秀明, 宮脇 哲, 越智 崇, 伊藤 明博, 鳥居征司, 齊藤 延人
    • Journal Title

      細胞分化・細胞死 オートファゴ ソーム/リソソーム由来の恒常的 ROS 産生が 酸化ストレス性神経細胞死に関与する(Celldifferentiation and death Implication of constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative cell death)(英語)(会議録)日本細胞生物学会大会講演要旨集 62回

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 細胞分化・細胞死 オートファゴ ソーム/リソソーム由来の恒常的 ROS 産生が 酸化ストレス性神経細胞死に関与する(Celldifferentiation and death Implication of constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative cell death)(英語)(会議録)2010

    • Author(s)
      鳥居 征司, 久保田 知里, 今井 英明 , 竹内 利行
    • Journal Title

      日本細胞生物学会大会講演要旨集

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Detection of compression vessels in trigeminal neuralgia by surface rendering 3D reconstruction of 1.5-T and 3.0-T MR imaging.

    • Author(s)
      M Shimizu, H Imai, K Kagoshima, E Umezawa, T Shimizu, Y Yoshimoto.
    • Journal Title

      World Neurosurg.

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ptosis as Partial Oculomotor Nerve Palsy Due to Compression by Infundibular Dilatation of Posterior Communicating Artery, Visualized With Three-dimensional Computer Graphics.

    • Author(s)
      Y Fukushima, H Imai, M Yoshino, T Kin,M Takasago, K Saito, H Nakatomi, N Saito.
    • Journal Title

      Neurol Med Chir (Tokyo)

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel modified method for injection into the cerebrospinal fluid via the cerebellomedullary cistern in mice.

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

      Acta Neurobiologiae Experimentalis

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Molecular imaging of rat hippocampus after transit global ischemia using imaging mass spectrometry2012

    • Author(s)
      S. Miyawaki, T. Hayasaka, H. Imai, H. Ono, H. Horikawa, T. Ochi A. Ito, H. Nakatomi, M. Setou, N. Saito
    • Organizer
      NEUROSCIENCE
    • Place of Presentation
      ニューオリンズ(アメリカ)
    • Related Report
      2012 Final Research Report
  • [Presentation] Revealing mechanisms of mitogen activated protein kinase phosphatase (MKP-1) under ischemic stress2012

    • Author(s)
      H. Horikawa, H. Imai, C. Murata, H. Ono, S. Miyawaki, T. Ochi, A. Ito, H. Nakatomi, S. Torii, N. Saito
    • Organizer
      NEUROSCIENCE
    • Place of Presentation
      ニューオリンズ(アメリカ)
    • Related Report
      2012 Final Research Report
  • [Presentation] Imaging mass spectrometry provides the comprehensive analysis of the dynamic change ofphospholipids in selective white matter injury of the rat model2012

    • Author(s)
      H. Ono, H. Imai, T. Hayasaka, S. Miyawaki,H. Horikawa, T. Ochi, A. Ito, M. Setou, N. Saito
    • Organizer
      NEUROSCIENCE
    • Place of Presentation
      ニューオリンズ(アメリカ)
    • Related Report
      2012 Final Research Report
  • [Presentation] Molecular imaging of rat hippocampus after transit global ischemia using imaging mass spectrometry2012

    • Author(s)
      S. MIYAWAKI, T. HAYASAKA, H. IMAI, H. ONO, H. HORIKAWA, T. OCHI, A. ITO, H. NAKATOMI, M. SETOU, N. SAITO
    • Organizer
      NEUROSCIENCE 2012
    • Place of Presentation
      New Orleans USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Revealing mechanisms of mitogen activated protein kinase phosphatase (MKP-1) under ischemic stress2012

    • Author(s)
      H. HORIKAWA, H. IMAI, C. MURATA, H. ONO, S. MIYAWAKI, T. OCHI, A. ITO, H. NAKATOMI, S. TORII, N. SAITO
    • Organizer
      NEUROSCIENCE 2012
    • Place of Presentation
      New Orleans USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Imaging mass spectrometry provides the comprehensive analysis of the dynamic change of phospholipids in selective white matter injury of the rat model2012

    • Author(s)
      H. ONO, H. IMAI, T. HAYASAKA, S. MIYAWAKI, H. HORIKAWA, T. OCHI, A. ITO, M. SETOU, N. SAITO
    • Organizer
      NEUROSCIENCE 2012
    • Place of Presentation
      New Orleans USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] MKP-1 mRNA and protein expression are induced after focal cerebral ischemia.2011

    • Author(s)
      H. Horikawa, H. Imai, Y. Chen, T. Ochi, A. Ito, H. Kanemitsu, H. Nakatomi, N. Saito.
    • Organizer
      Brain
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2011-05-27
    • Related Report
      2012 Final Research Report
  • [Presentation] Focal cerebral ischemia models of both lissencephalic and gyrencephalic species2011

    • Author(s)
      H. Imai, N. Saito.
    • Organizer
      Brain
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2011-05-25
    • Related Report
      2012 Final Research Report
  • [Presentation] FOCAL CEREBRAL ISCHEMIA MODELS OF BOTH LISSENC EPHALIC AND GYRENCEPHALIC SPECIES2011

    • Author(s)
      H.Imai, N.Saito
    • Organizer
      Brain 2011
    • Place of Presentation
      バルセロナ(スペイン)(招待講演)
    • Year and Date
      2011-05-25
    • 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
    • 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
    • Related Report
      2012 Final Research Report

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Published: 2010-11-30   Modified: 2019-07-29  

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