| Project/Area Number |
03404028
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
KATO Hiroyuki (1992-1993) TOHOKU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (60224531)
小暮 久也 (1991) 東北大学, 医学部, 教授 (20133936)
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| Co-Investigator(Kenkyū-buntansha) |
ONODERA Hiroshi TOHOKU UNIVERSITY HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (20214207)
ABE Koji TOHOKU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (20212540)
NAKAMURA Syozo TOHOKU UNIVERSITY HOSPITAL, LECTURER, 医学部・附属病院, 講師 (80108498)
加藤 宏之 東北大学, 医学部, 助手 (60224531)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1991: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Cerebral ischemia / Vascular dementia / Molecular biology / Heat shock proteins / Stress response / 熱ショック蚕白 / 熱ショック蛋白質 / in situ hybrldization |
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| Research Abstract |
We investigated the mechanisms of cerebrovascular dementia using experimental animal models with molecular biological techniques. Results obtained are as follows. (1) We demonstrated that cerebral ischemia gives rise to altered gene expressions in selectively vulnerable neurons in brains of gerbils and rats. We used cDNA probes for heat shock protein-70 (HSP70) and heat shock cognate protein-70 (HSC70) cloned from ischemic gerbil brains and performed in situ hybridization. In gerbils, loss of HSP70 mRNA and HSP70 protein preceded CA1 neuronal death, which suggested the role of transcriptional and translational disturbances in ischemic neuronal death. In contrast, neuronal death occurred in face of HSP70 synthesis in the rat. (2) We also investigated the mechanisms of ischemic tolerance that is induced after preconditioning with sublethal ischemia. The amount of excitotory amino acid glutamate released during ischemia as measured with intracerebral microdialysis was not altered by preconditioning. However, the role of HSP70 was suggested because temporal profile of HSP70 expression was similar to that of ischemic tolerance and because the tolerance was inhibited by treatment with anti-HSP70 antibody or quercetin, an inhibitor of HSP expression. We observed facilitated induction of HSP70 mRNA and protein in the tolerance-acquired brain. In rat brain with ischemic tolerance, HSP27 was induced predominantly in glial cells, suggesting neuroprotection through neuron-glia interaction. Thus, the findings strongly suggest that cerebral ischemia induced gene expressions in neurons and glial cells, thereby activating direct and indirect systems of neuroprotection against injury.
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