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Treatment for acute/chronic ischemic neuronal injury using vanadate

Research Project

Project/Area Number 15591534
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MORIOKA Motohiro  Kumamoto University, Neurosurgery, Instructor, 医学部附属病院, 講師 (20295140)

Co-Investigator(Kenkyū-buntansha) HAMADA Jun-ichiro  Kumamoto University, Neurosurgery, Instructor, 医学部附属病院, 講師 (40253752)
GOTO Satoshi  Kumamoto University, Neurosurgery, Assistant Professor, 大学院・医学薬学研究部, 助教授 (50240916)
KAI Yutaka  Kumamoto University, Neurosurgery, Assistant, 大学院・医学薬学研究部, 助手 (30322308)
YANO Shigetoshi  Kumamoto University, Neurosurgery, Assistant, 医学部附属病院, 助手 (60332871)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsischemia / MCA occlusion / vanadate / apoptosis / Akt / ERK
Research Abstract

Orthovanadate is a competitive inhibitor of protein tyrosine phosphatases. Some of its reported biologic effects are its insulin mimetic property and its activation of phosphoinositide 3-kinase and extracellular-signal regulated kinase(ERK). The authors previously reported its neuroprotective effect on delayed neuronal death of gerbil hippocampal CA1 neurons via Akt and ERK activation after transient forebrain ischemia. In the present study, the neuroprotective effect of postischemic intraperitoneal administration of sodium orthovanadate(2 l/kg of 50-mmol/l sodium orthovanadate in saline) was investigated in rats with transient middle cerebral artery occlusion. Ischemic neuronal injury was evaluated 1 day and 28 days after ischemia. The neuroprotective effect of orthovanadate was significant in the cortex but not the caudate putamen(ischemic core) at both 1 and 28 days after ischemia. In orthovanadate group, the activities of Akt and ERK were maintained after reperfusion ; they were decreased in saline group. Blood glucose level decreased but within normal range.
Regional cerebral blood flow was lower than that of saline group only at 0 hours after reperfusion. These data suggest that orthovanadate has neuroprotective effects in rats with transient middle cerebral artery occlusion and that these effects are mediated by Akt and ERK activation. Furthermore, low blood glucose levels and gradual recovery of regional cerebral blood flow may contribute to neuroprotection.
Next, we injected vanadte after ischemia. The number of Budr/double cortin positive cells decreased remarkably in SVZ. Thus we concluded that vanadate induced progenitor cells after ischemia.
Vanadate may have a potential that induced neuronal regeneration. Further investigation and trial for treatment were needed.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2004 2003 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] The post-ischemic administration of DY-9760e), a novel calmodulin antagonist, prevents delayed neuronal death in gerbil hippocampus.2004

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

      J Pharmacol Sci 96

      Pages: 65-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke : Their role in the formation of stable and unstable carotid atherosclerotic plaques.2004

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

      Surgical Neurology 62

      Pages: 292-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto Prefecture, Japan.2004

    • Author(s)
      Hamada J. et al.
    • Journal Title

      Neurosurgery 54

      Pages: 31-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus.2004

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

      Journal of Cerebral Blood Flow and Metabolism 24

      Pages: 271-279

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP.2004

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

      Cell Death and Differentiation 11

      Pages: 403-415

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain stem venous congestion due to dural arteriovenous fistulas of the cavernous sinus.2004

    • Author(s)
      Kai, Y., Hamada J.-I., Morioka M., Yano S., Ushio
    • Journal Title

      Acta Neurochir(Wien) 146

      Pages: 1107-1112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The post-ischemic administration of 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1h-indazole dihydrochloride 3.5 hydrate(DY-9760e), a novel calmodulin antagonist, prevents delayed neuronal death in gerbil hippocampus.2004

    • Author(s)
      Hashiguchi, A., Yano, S., Morioka, M., Hamada, J., Shirasaki Y, Kochi M, Fukunaga, K.
    • Journal Title

      J Pharmacol Sci 96

      Pages: 65-72

    • NAID

      10014166332

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke : Their role in the formation of stable and unstable carotid atherosclerotic plaques.2004

    • Author(s)
      Morioka, M., Hamada, J., Hashiguchi, A., Hasegawa, Y., Todaka, T., Yano, S., Kai, Y., Miura, M., Fujioka, S, Ushio, Y.
    • Journal Title

      Surgical Neurology 62

      Pages: 292-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto Prefecture, Japan.2004

    • Author(s)
      Hamada, J., Morioka, M., Yano, S., Kai, Y., Ushio, Y.
    • Journal Title

      Neurosurgery 54

      Pages: 31-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus.2004

    • Author(s)
      Hashiguchi, A., Yano, S., Morioka, M., Hamada, J., Ushio, Y., Takeuchi, Y., Fukunaga, K.
    • Journal Title

      J of Cerebral Blood Flow and Metabolism 24

      Pages: 271-279

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP.2004

    • Author(s)
      Tajiri, S., Oyadomari, S., Yano, S., Morioka, M., Gotoh, T., Hamada, J., Ushio, Y., Mori, M.
    • Journal Title

      Cell Death and Differentiation 11

      Pages: 403-415

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The post-ischemic administration of DY-9760e), a novel calmodulin antagonist, prevents delayed neuronal death in gerbil hippocampus.2004

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

      J Pharmacol Sci 96

      Pages: 65-72

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto Prefecture, Japan.2004

    • Author(s)
      Hamada J.et al.
    • Journal Title

      Neurosurgery 54

      Pages: 31-73

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus.2004

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

      Journal of Cerebral Blood Flow and Metabolism 24

      Pages: 271-279

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP.2004

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

      Cell Death and Differentiation 11

      Pages: 403-415

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multimodal treatment of ruptured dissecting aneurysms of the vertebral artery during the acute stage.2003

    • Author(s)
      Hamada, J., Kai, Y., Morioka, M., Yano, S., Todaka, T, Ushio, Y.
    • Journal Title

      Journal of Neurosurgery 99

      Pages: 960-966

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tajiri S, Oyadomari S, Yano S, Morioka M et al.: "Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP"Cell Death Differ.. 11(4). 403-415 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] J Hamada, Kai Y, M Morioka, et al.: "Multimodal treatment of ruptured dissecting aneurysms of the vertebral artery during the acute stage"J Neurosurg.. 99. 960-966 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hasegawa Y, Hamada J, Morioka M, et al.: "Neuroprotective effect of postischemic administration of sodium orth ovanadate in rats with transient middle cerebral artery occlusion"J Cereb Blood Flow Metab.. 23. 1040-1051 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T Hara, J Hamada, S Yano, M Morioka, et al.: "CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region"J.Neurochem.. 86. 805-814 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Morioka, et al.: "The angiographical dilatation and branch extension of the AchA and P-CoM artery are predictors of hemorrhage in adult moyamoya patients"Stroke. 34. 90-95 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Morioka, et al.: "High-risK age for rebleeding in patients with hemorrhagic moyamoya disease : Long-term follow-up study"Neurosurgery. 52. 1049-1055 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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