| Project/Area Number |
14572088
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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 |
Biological pharmacy
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| Research Institution | Fukuyama University |
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Principal Investigator |
TAMURA Yutaka Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Associate professor, 薬学部, 助教授 (30217202)
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| Co-Investigator(Kenkyū-buntansha) |
AMANO Taku Hiroshima University, School of Medicine, Assistant professor, 医学部, 助手 (10294547)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | adenosine / dementia / gerbil / ischemia / neuroprotection / primary culture / adenosine / AMP / ATP / A1 receptor / cortex / culture / glutamte / necrosis |
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| Research Abstract |
Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal cell death were examined by using ischemic animal model and primary culture.
Transient bilateral carotid occlusion in gerbil caused a selective delayed degeneration of the pyramidal neurons in the CA1 hippocampal area. This selective damage was attenuated by MK-801, a NMDA receptor antagonist and L-NAME, a nitric oxide synthase inhibitor. Moreover, CHA, an adenosine A1 receptor antagonist and CGS-21680, an adenosine A2 receptor antagonist, were also effective in protection of CA1 pyramidal neurons.
The neuronal cell death caused, when the primary culture cell was incubated in hypoxia and hypoglycemia solution. This cell death was attenuated by treatment of MK-801, L-NAME, adenosine, CHA and CGS-21680. CHA reduced hypoxia/hypoglycemia-induced elevation of intracellular Ca2+ level. Neuroprotective effects of CGS-20680 was attenuated by H-89, a protein kinase A inhibitor.
These results indicate that adenosine is endogenous neuroprotection substance against ischemic neuronal cell death. Moreover, this results rise the possibility that adenosine becomes a drug for the dementia induced by vascular damage.
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