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Regenerative medicine for cerebral infarction: Stem cell transplantation in the rat model of middle cerebral artery occlusion

Research Project

Project/Area Number 17590877
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionShimane University

Principal Investigator

NAGAI Atsushi  Shimane University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40273940)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Shotai  Shimane University, Faculty of Medicine, Dean of Hospital, 医学部, 院長 (00118811)
TERASHIMA Masaharu  Shimane University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40227517)
MASUDA Junichi  Shimane University, Faculty of Medicine, Professor, 医学部, 教授 (70173747)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordscerebral infarction / regenerative medicine / cell transplantation / stem cells / neurotrophic factors / stroke medel rat / apoptosis / 移植 / 神経保護 / 炎症 / リアルタイムPCR / 脳梗塞モデルラット / 神経幹細胞 / 骨髄間葉系幹細胞 / ミクログリア / 栄養因子 / サイトカイン
Research Abstract

Cerebral stroke frequently occurs in Japanese elderly people and lowers quality of life of the patients. Functional recovery is rarely seen, so the increasing number of the patients is one of the major problems in the modern society. Regenerative medicine may induce the regeneration of disturbed neurons and give us hope for functional recovery even after cerebral stroke. We made a stroke model of middle cerebral artery occlusion in rats with nylon suture method. At Day 1-2, human-derived neuronal cell line, such as neural stem cell line (F3), mesenchymal stem cell line (HB10) and microglial cell line (HMO) was intravenously injected. The transplantation significantly improve the symptom evaluated with the Neurological Severity Score after Day 7. Transplanted cells migrated into the stroked brain; at Day 3, every type of injected cells was seen in stroke border zone area, but at Day 7, HB10 cells and HMO cells already disappeared there. Only F3 cells survived until Day 14. TUNEL stainin … More g indicated that transplantation decreased the apoptotic cells found in the area, which may mean neuroprotection by transplanted cells. Molecular biological analysis was performed to evaluate expressional level of neurotrophic factors. Rat-derived neurotrophic factors such as epidermal growth factor, insulin-like growth factor-1 and granulocyte-colony stimulating factor significantly increased in the penumbra area compared to human-derived growth factors. Inflammatory factors were also investigated with immnohistochemistry after F3 transplantation. Cyclooxygenase-2 (Cox-2) expression was decreased in the infiltrated macrophages and activated microglia in the penumbra area. Iducible nitric oxide synthase (iNOS) expression was also decreased in the endothelial cells. F3 transplantation decreased the number of infiltrated neutrophils around the stroke area, leading to inhibit the inflammatory reaction. In the present study, we demonstrated the several mechanisms why cell transplantation induced recovery from cerebral infarction using rat stroke model. We also presented in the conferences and published the articles about the stroke during the two years. We are further undergoing our study to understand the mechanism of cerebral infarction and neuroprotection by the cell regenerative therapy Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005

All Journal Article (18 results)

  • [Journal Article] 脳アミロイドアンギオパチー2006

    • Author(s)
      長井 篤
    • Journal Title

      EBMに基づく脳神経疾患の基本治療指針(改訂第2版)

      Pages: 54-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease : astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase2006

    • Author(s)
      Ishida, Y
    • Journal Title

      J Neuropathol Exp Neurol 65

      Pages: 66-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 骨髄間葉系幹細胞による脳出血再生医療2006

    • Author(s)
      長井 篤
    • Journal Title

      分子脳血管病 5

      Pages: 429-435

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] プロテアーゼとプロテアーゼインヒビター-髄液中視ステインプロテアーゼおよびシスタチンC濃度と中枢神経疾患の関連性-2006

    • Author(s)
      長井 篤
    • Journal Title

      島根医学検査 34・1

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease : as trocyte-mediated neuroprotection through increased levels of glutathione peroxidase2006

    • Author(s)
      Ishida Y, et al.
    • Journal Title

      J Neuropathol Exp Neurol 65

      Pages: 66-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease : astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase2006

    • Author(s)
      Ishida, Y
    • Journal Title

      J Neuropathol Exp Neurol, 65

      Pages: 66-77

    • Related Report
      2006 Annual Research Report
  • [Journal Article] (Mini-Review) Immortalized Human Microglial Cell Line : Phenotypic Expression.2005

    • Author(s)
      Nagai A
    • Journal Title

      Journal of Neuroscience Research 81

      Pages: 342-348

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] アルツハイマー病における1H-MRSと海馬面積の関連2005

    • Author(s)
      小黒 浩明
    • Journal Title

      老年精神医学雑誌 16・7

      Pages: 847-852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 第9章てんかん発作、10.精神状態の受容、11.めまいと失調、12.急性視覚障害、13.脊髄圧迫2005

    • Author(s)
      長井 篤
    • Journal Title

      WM臨床研修サバイバルガイド(神経内科)(小林祥泰監訳)

      Pages: 129-179

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 前頭葉実行機能に対する情動障害(うつ、アパシー)の影響-Frontal Assessment Batteryを用いた検討-2005

    • Author(s)
      山口 修平
    • Journal Title

      認知神経科学 7・3

      Pages: 256-260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B.2005

    • Author(s)
      Nagai A
    • Journal Title

      Brain Reseach 1066

      Pages: 120-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 糖尿病合併脳卒中の臨床的特徴と予後 -Japanese standard stroke Registry Study (JSSRS)の結果より-2005

    • Author(s)
      卜蔵 浩和
    • Journal Title

      脳と神経 58・2

      Pages: 135-139

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immortalized Human Microglial Cell Line : Phenotypic Expression. (Mini-Review)2005

    • Author(s)
      Nagai A, et al.
    • Journal Title

      Journal of Neuroscience Research 81

      Pages: 342-348

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B.2005

    • Author(s)
      Nagai A, et al.
    • Journal Title

      Brain Reseach 1066

      Pages: 120-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] (Mini-Review)Immortalized Human Microglial Cell Line : Phenotypic Expression.2005

    • Author(s)
      Nagai A
    • Journal Title

      Journal of Neuroscience Research 81

      Pages: 342-348

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 第9章てんかん発作、10.精神状態の受容、11.めまいと失調、12.急性視覚障害、13.脊髄圧迫2005

    • Author(s)
      長井 篤
    • Journal Title

      (WM臨床研修サバイバルガイド)神経内科(小林祥泰監訳)

      Pages: 129-179

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with catheps in B.2005

    • Author(s)
      Nagai A
    • Journal Title

      Brain Reseach 1066

      Pages: 120-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 糖尿病合併脳卒中の臨床的特徴と予後-Japanese Standard Stroke Registry Study(JSSRS)の結果より-2005

    • Author(s)
      卜蔵 浩和
    • Journal Title

      脳と神経 58・2

      Pages: 135-139

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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