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Identification and analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays

Research Project

Project/Area Number 16591793
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionOsaka University

Principal Investigator

HOSOKAWA Ko  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20181498)

Co-Investigator(Kenkyū-buntansha) YANO Kenji  Osaka University, Gradate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40174560)
久保 盾貴  大阪大学, 医学系研究科, 助手 (00362707)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsperipheral nerve regeneration / sciatic nerve / cyclin-dependent kinase inhibitor p21 / Rho kinase inhibitor / fasudil / Slit-Robo / facial nerve / slit / growth cone / 反発因子 / in situ hybridization / radial growth / neurofilament
Research Abstract

It is generally known that injured peripheral axons regenerate successfully as oppose to central axons. However, complete functional recovery is rarely achieved. To solve this problem, we identified 500 genes induced in peripheral nerve after axotomy using cDNA microarrays in a previous study. The purpose of this project was to analyze the precise function of these genes. The main findings were as follows. 1. Sciatic nerve injury models were created on the p21 knock out mice and it was found that p21, which is a potent Rho kinase inhibitor, regulates radial growth of regenerating axons, thereby promoting functional recovery. Hyperphosphorylation of the neurofilament heavy chain subunits was considered to be the main reason for the impaired radial growth in the p21 knock out mice. 2. The clinically tested Rho-associated kinase inhibitor fasudil hydrochloride was applied to rat peroneal nerve injury models. After injury, significantly accelerated functional recovery was achieved in the fasudil treated animals as compared with control animals. 3. The mRNA expression changes of Slit-Robo signal molecules, known as axonal guidance cues, were examined using in situ hybridization. After transection of a rat facial nerve, up-regulation of slitl expression and down-regulation of slit2 expression were found in the facial nucleus. In contrast, both expressions were up-regulated in the distal Schwann cells.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2007 2006 Other

All Journal Article (5 results)

  • [Journal Article] The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system.2007

    • Author(s)
      Madura T
    • Journal Title

      Plastic and Reconstructive Surgery 119(2)

      Pages: 526-535

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system.2007

    • Author(s)
      Madura T et al.
    • Journal Title

      Plastic and Reconstructive Surgery 119(2)

      Pages: 526-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] P21^<Cipl/WAF> regulates radial growth and enhances motor functional recovery in the injured peripheral nervous system.2006

    • Author(s)
      Tomita K
    • Journal Title

      Brain research 1081(1)

      Pages: 44-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] P21^<Cip1/WAF> regulates radial growth and enhanoes motor functional recovery in the injured peripheral nervous system.2006

    • Author(s)
      Tomita K et al.
    • Journal Title

      Brain research 1081(1)

      Pages: 44-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] P21^<Cip1/WAF> regulates radial growth and enhance motor functional recovery in the injured peripheral nervous system

    • Author(s)
      Tomita K
    • Journal Title

      Brain Research 発表予定(in press)

    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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