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2007 Fiscal Year Final Research Report Summary

Angiogenesis therapy against cerebral ischemic disease

Research Project

Project/Area Number 17591521
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOita University

Principal Investigator

KOBAYASHI Hidenori  Oita University, Faculty of Medicine, Professor (80126581)

Co-Investigator(Kenkyū-buntansha) HIKAWA Takamitsu  Oita University, Faculty of Medidne, Lecturer (20238257)
MORISHIGE Masaki  Oita University, Facility of Medicine, Research Associate (60381050)
Project Period (FY) 2005 – 2007
KeywordsHIF-1 α / Cerebral Infarction / VEGF / Ischemic Tolerance / GGA / HSP-70 / Angiogenesis / Hypoxia
Research Abstract

Hyoxia-inducible factor 1(HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1α, which accumulates under hypmic conditions, and constitutively expressed subunit, HIF-1β. We investigated HIF-1α naked DNA-induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis model and inoculated HIF-1α naked DNA on the brain surface or temporal muscle. We analyzed HIF-1α induced angiogenic factors and collateral circulation. A histological section treated with HIF-1α DNA showed an increased expression of HIF-1α and VEGF with collateral circulation, in comparison with control DNA HIF-1α transcription factor is able to promote significant angiogenesis development.
Geranylgeranylacetone (GGA) is known as an antinuclear agent and more recently as a heat shock protein (HSP) inducer. This study evaluated the neuroprotective effect of GGA against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion in rats. GGA was given orally in various regimens prior to MCA ocdusion Pretreatment with a single oral GGAdose (800 mg/kg) 48 hours before ischemia significantly attenuated cerebral infarction volume. A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.

  • Research Products

    (24 results)

All 2008 2006 2005

All Journal Article (24 results) (of which Peer Reviewed: 12 results)

  • [Journal Article] GEP 100 links epidermal growth factor receptor signaling to Arf6 activation to induce breast cancer invasion2008

    • Author(s)
      Morishige M
    • Journal Title

      Nature Cell Biol 10

      Pages: 85-92

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] GEP 100 links epidermal growth factor receptor signaling to Arf6 activation to induce breast cancer invasion2008

    • Author(s)
      Morishige, M., Hashimoto, S., Ogawa, E., Toda, Y., Kotani, H., Hirose, M., Wei, S., Hashimoto, A., Yamada, A., Yano, H., Mazaki, Y., Kodama, H., Nio, Y., Manabe, T., Wada, H., Kobayashi, H., Sabe, H.
    • Journal Title

      Nature Cell Biol 10

      Pages: 85-92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 血管新生研究と脳神経外科治療への展開2006

    • Author(s)
      阿部 竜也
    • Journal Title

      脳神経外科 34

      Pages: 123-132

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Intraoperative corticomuscular motor evoked potentials for evaluation of motor function:a comparison with corticospinal D and I waves2006

    • Author(s)
      Fujiki M
    • Journal Title

      J Neurosurg 104

      Pages: 85-92

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment2006

    • Author(s)
      Fujiki M
    • Journal Title

      Neurosci Lett 405

      Pages: 226-230

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of protein kinase C in neuropotective effect of geranylgeranylacetone,a noninvasive inducing agent of heat shock protein,on delayed neuronal death caused by transient ischemia in rats2006

    • Author(s)
      Fujiki M
    • Journal Title

      J Neurotrauma 23

      Pages: 1164-1178

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Geranylgeranylacetone,a noninvasive heat shock protein inducer,induces protein kinase C and leads to neuroprotection against cerebral infarction in rats2006

    • Author(s)
      Uchida S
    • Journal Title

      Neurosci Lett 396

      Pages: 220-224

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model2006

    • Author(s)
      Anan M
    • Journal Title

      Neurosci Lett

      Pages: 118-123

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 血管新生研究と脳神経外科治療への展開2006

    • Author(s)
      阿部, 竜也, 上田, 徹, 藤木, 稔, 古林, 秀則
    • Journal Title

      脳神経外科 34(2)

      Pages: 123-132

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intraoperative corticomuscular motor evoked potentials for evaluation of motor function : a comparison with cortico-spinal D and I waves-2006

    • Author(s)
      Fujiki, M., Furukawa, Y., Kamida, T., Anan, M., Inoue, R., Abe, T., Kobayashi, H.
    • Journal Title

      J Neurosurg 104

      Pages: 85-92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment2006

    • Author(s)
      Fujiki, M., Hikawa, T., Abe, T., Ishii, K., Kobayashi, H.
    • Journal Title

      Neurosci Lett 405

      Pages: 226-230

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of protein kinase C in neuropotective effect of geranylgeranylacetone, a noninvasive inducing agent of heal shock protein, on delayed neuronal death caused by transient ischemia in rats2006

    • Author(s)
      Fujiki, M., Hikawa, T., Abe, T., Uchida, S., Morishige, M., Sugita, K., Kobayashi, H.
    • Journal Title

      J Neurotrauma 23(7)

      Pages: 1164-1178

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein kinase C and leads to neuroprotection against cerebral infarction in rats2006

    • Author(s)
      Uchida, S., Fujiki, M., Nagai, Y., Abe, T., Kobayashi, H.
    • Journal Title

      Neurosci Lett 396(3)

      Pages: 220-224

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induced angiogenesis under cerebral ischemia by cyclo-oxygenase 2 and hypoxia-inducible factor naked DNA in a To indirect-bypass model2006

    • Author(s)
      Anan, M., Abe, T., Matsuda, T., Ishii, K., Kamida, T., Fujiki, M., Kobayashi, H.
    • Journal Title

      Neurosci Lett 409(2)

      Pages: 118-123

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neuroprotective effect of geranylgeranylacetone:a noninvasive heat shock protein inducer on cerebral infarction in rats2005

    • Author(s)
      Nagai Y
    • Journal Title

      Neurosci Lett 374

      Pages: 183-188

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Mutant IκB_α suppresses hypoxia-induced VEGF expression through down-regulation of HIF-1α and COX-2 in human glioma cells2005

    • Author(s)
      Kimba Y
    • Journal Title

      Oncol Res 15

      Pages: 139-149

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Hypoxia-lnducible factor-1α DNA Induced angiogenesis in a rat cerebral Ischemic model2005

    • Author(s)
      Matsuda T
    • Journal Title

      Neurol Res 27

      Pages: 503-508

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Geranylgeranylacetone limits secondary injury, neuronal death,and progressive necrosis and cavitation after spinal cord injury2005

    • Author(s)
      Fujiki M
    • Journal Title

      Brain Res 1053

      Pages: 175-184

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neuroprotective effect of Donepezil,a nicotinic acetylcholine-receptor activator,on cerebral infarction in rats2005

    • Author(s)
      Fujiki M
    • Journal Title

      Brain Res 1043

      Pages: 236-241

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neuroprotective effect of geranylgeranylacetone : a noninvasive heat shock protein inducer on cerebral infarction in rats2005

    • Author(s)
      Nagai, Y., Fujiki, M., Inoue, R., Uchida, S., Abe, T., Kobayashi, H., Cetinalp, NE.
    • Journal Title

      Neurosci Lett 374(3)

      Pages: 183-188

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutant I κBα, suppresses hypoxia-induced VEGF expression Through down-regulation of HIF-1 α and COX-2 in human glioma cells2005

    • Author(s)
      Kimba, Y., Abe, T., Wu, JL., Inoue, R., Fujiki, M., Kohno, K., Kobayashi, H.
    • Journal Title

      Oncol Res 15

      Pages: 139-149

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypoxia-Inducible factor-1α DNA Induced angiogenesis in a rat cerebral Ischemic model2005

    • Author(s)
      Matsuda, T., Abe, T., Wu, JL., Fujiki, M., Kobayashi, H.
    • Journal Title

      Neurol Res 27(7)

      Pages: 503-508

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Geranylgeranylacetone limits secondary injury, neuronal death, and progressive necrosis and cavitation after spinal cord injury2005

    • Author(s)
      Fujiki, M., Furukawa, Y., Kobayashi, H., Abe, T., Ishii, K.
    • Journal Title

      Brain Res 1053(1-2)

      Pages: 175-184

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neuroprotective effect of Donepezil, a nicotinic acetylcholine-receptor activator, on cerebral infarction i rats2005

    • Author(s)
      Fujiki, M., Kobayashi, H., Uchida, S., Inoue, R., Ishii, K.
    • Journal Title

      Brain Res 1043(1-2)

      Pages: 236-241

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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