2004 Fiscal Year Final Research Report Summary
Treatment for acute/chronic ischemic neuronal injury using vanadate
| Project/Area Number |
15591534
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
MORIOKA Motohiro Kumamoto University, Neurosurgery, Instructor, 医学部附属病院, 講師 (20295140)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | ischemia / MCA occlusion / vanadate / apoptosis / Akt / ERK |
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| 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.
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[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.
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Journal Title
J Pharmacol Sci 96
Pages: 65-72
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Surgical Neurology 62
Pages: 292-303
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Neurosurgery 54
Pages: 31-73
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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.
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Journal Title
Cell Death and Differentiation 11
Pages: 403-415
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Journal of Neurosurgery 99
Pages: 960-966
Description
「研究成果報告書概要(欧文)」より
