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Neural stem/progenitor cell transplantation therapy for perinatal brain damage.

Research Project

Project/Area Number 16591084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center

Principal Investigator

NAKANISHI Keiko  Inst. Dev. Res., Dept. Perinatology, senior scientist, 周生期学部, 主任研究員 (50280813)

Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsprenatal brain damage / hypoxic-ischemic encephalopathy / hypoxia-ischemia model / neural stem / progenitor cells / neural cell death / chondroitin sulfate / glutamate toxicity / 細胞外マトリックス / 神経保護因子 / プロテオグリカン
Research Abstract

Perinatal hypoxia-ischemia (HI) remains a critical issue affecting 2-3 of 1000 live births in developed countries, with no effective treatments except brain hypothermia. This project is aimed to examine whether neural stem/progenitor cell (NSPC) transplantation therapy may have therapeutic effect for perinatal HI. We produced neonatal HI rats by exposure to hypoxia following ligation of the right common carotid artery, and injected NSPCs into the right ventricle 24 hours after hypoxia. There was no difference between vehicle-and NSPC-injected rats in the wet weight of the right cerebral hemisphere measured 7 days after injection. When the rats were treated with NSPC combined with chondroitinase, which digests glycosaminoglycans of chondroitin sulfate proteoglycan, cerebral damage was significantly reduced. There was no obvious effect in chondroitinase-treated rats without NSPCs. Although we need further investigation, there is a possibility that intracerebral injection of NSPCs with chondroitinase may become a useful therapy for neonatal HI. Next, to elucidate a candidate for preventing neuronal cell death, we cultured rat neocortical neurons and examined NMDA-induced excitatory neuronal cell death. Preadministration of a highly sulfated chondroitin sulfate (CS) preparation, CS-E, significantly reduced neuronal cell death induced by NMDA, but other CS preparations such as CS-A, CS-B, CS-C, and CS-D, did not. These results indicate that CS-E may be a good candidate for neural cell protection.

Report

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

    (26 results)

All 2007 2006 2004 Other

All Journal Article (20 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] NKCC1 activity modulates formation of functional inhibitory synapses in cultured neocortical neurons.2007

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

      Synapse 61(3)

      Pages: 138-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NKCC1 activity modulates formation of functional inhibitory synapses in cultured neocortical neurons.2007

    • Author(s)
      Nakanishi K, et al.
    • Journal Title

      Synapse 61(3)

      Pages: 138-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Identification and functions of chondroitin sulfate in the milieu of neural stem cells.2006

    • Author(s)
      Ida et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 5982-5991

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of neurite outgrowth-promoting domains of Neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatidylinositol 3-kinase and protein kinase C signaling pathways in neuritogenesis.2006

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

      J. Biol. Chem. 281

      Pages: 24970-24978

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats2006

    • Author(s)
      Kakizawa H et al.
    • Journal Title

      Early Human Development (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification and functions of chondroitin sulfate in the milieu of neural stem cells.2006

    • Author(s)
      Ida M, et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 5982-5991

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of neurite outgrowth-promoting domains of Neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatidylinositol 3-kinase and protein kinase C signaling pathways in neuritogenesis.2006

    • Author(s)
      Nakanishi K, et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 24970-24978

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of neurite outgrowth-promoting of Neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatidylinositol 3-kinase and protein kinase C signaling pathways in neuritogenesis.2006

    • Author(s)
      Nakanishi K, et al.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 24970-24978

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats2006

    • Author(s)
      Kakizawa H, et al.
    • Journal Title

      Early Human Development (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification and functions of chondroitin sulfate in the milieu of neural stem cells.2006

    • Author(s)
      Ida M, et al.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 5982-5991

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Altered synaptic activities in culture of neocortical neurons from prenatally X-irradiated rats.2004

    • Author(s)
      Nakanishi A et al.
    • Journal Title

      Neurosci. Lett. 355

      Pages: 61-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glycosilation site for chondroitin sulfate on the neural part-time proteoglycan, Neuroglycan C.2004

    • Author(s)
      Aono S et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 46536-46541

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroglycan C, a brain-specific part-time proteoglycan, with a particular multidomain structure.2004

    • Author(s)
      Oohira A et al.
    • Journal Title

      Glycoconjugate J., 21, 53-57, 2004. 21

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Altered synaptic activities in culture of neocortical neurons from prenatally X-irradiated rats.2004

    • Author(s)
      Nakanishi K, et al.
    • Journal Title

      Neurosci. Lett. 355

      Pages: 61-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glycosilation site for chondroitin sulfate on the neural part-time proteoglycan, Neuroglycan C.2004

    • Author(s)
      Aono S, et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 46536-46541

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroglycan C, a brain-specific part-time proteoglycan, with a particular multidomain structure.2004

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

      Glycoconjugate J. 21

      Pages: 53-57

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Altered synaptic activities in culture of neocortical neurons from prenatally X-irradiated rats.2004

    • Author(s)
      Nakanishi K, Watanabe K, Kawabata M, Fukuda A, Oohira A.
    • Journal Title

      Neurosci.Lett. 355

      Pages: 61-64

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Glycosilation site for chondroitin sulfate on the neural part-time proteoglycan, Neuroglycan C.2004

    • Author(s)
      Aono S, Tokita Y, Shuo T, Yamauchi S, Matsui F, Nakanishi K, Hirano K et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 46536-46541

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroglycan C, a brain-specific part-time proteoglycan, with a particular multidomain structure.2004

    • Author(s)
      Oohira A, Shuo T, Tokita Y, Nakanishi K, Aono S.
    • Journal Title

      Glycoconjugate J. 21

      Pages: 53-57

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats.

    • Author(s)
      Kakizawa H, et al.
    • Journal Title

      Early Human Development (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許権2006

    • Inventor(s)
      中西圭子, 大平敦彦, 佐藤義朗, 前田 浩
    • Industrial Property Rights Holder
      愛知県・生化学工業株式会社
    • Industrial Property Number
      2006-139843
    • Filing Date
      2006-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許権2006

    • Inventor(s)
      中西圭子, 大平敦彦, 佐藤義朗, 前田 浩
    • Industrial Property Rights Holder
      愛知県・生化学工業株式会社
    • Industrial Property Number
      2006-139813
    • Filing Date
      2006-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許権「脳損傷抑制剤」2006

    • Inventor(s)
      中西 圭子, 大平 敦彦, 佐藤 義朗, 前田 浩
    • Industrial Property Rights Holder
      愛知県・生化学工業株式会社
    • Industrial Property Number
      2006-139843
    • Filing Date
      2006-05-19
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権「神経細胞の細胞死抑制剤等」2006

    • Inventor(s)
      中西 圭子, 大平 敦彦, 佐藤 義朗, 前田 浩
    • Industrial Property Rights Holder
      愛知県・生化学工業株式会社
    • Industrial Property Number
      2006-139813
    • Filing Date
      2006-05-19
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2004

    • Inventor(s)
      中西圭子, 大平敦彦, 青野幸子
    • Industrial Property Rights Holder
      生化学工業株式会社
    • Industrial Property Number
      2004-228693
    • Filing Date
      2004-08-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許権2004

    • Inventor(s)
      中西 圭子, 青野 幸子, 大平 敦彦
    • Industrial Property Rights Holder
      生化学工業株式会社
    • Industrial Property Number
      2004-228693
    • Filing Date
      2004-08-04
    • Related Report
      2004 Annual Research Report

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

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