| Project/Area Number |
63570370
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
MIHARA Ban (1990-1991) School of medicine, Keio University Instructor, 医学部, 助手 (30190721)
高嶋 修太郎 (高嶋・修太郎) (1988-1989) 慶応義塾大学, 医学部・内科, 助手 (50146586)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAI Toshitaka School of medicine, Keio University Instructor, 医学部, 助手 (80196592)
美原 盤 慶応義塾大学, 医学部・内科, 助手 (30190721)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Neurotransmission / Second-Messenger / Adenylate Cyclase / Protein Kinase C / Cerebral Ischemia / Local Cerebral Bood Flow / 局所脳血流量 / アデニレ-ト・サイクレ-ス / プロテインキナ-ゼC / 脳梗塞 / 学習能力 / アデニレート・サイクレース / プロテインキナーゼC |
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| Research Abstract |
Alterations of the second-messenger systems, adenylate cyclase (AC) and protein kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during experimental cerebral ischemia in gerbils employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. Ischemia was induced by occlusion of the right common carotid artery for 6 hours. Animals attaining more than 5 in their ischemic scores were utilized for further experiments. At the end of ischemia, lCBF was measured by the [ ^<14>C]iodoantipyrine method. The AC and PKC activities were estimated by the agtoradiographic technique developed in our laboratory using[ ^3H]forskolin (FK) and [ ^3H]phorbol 12, 13dibutyrate (PDBu), respectively. The lCBF fell below 10 ml/100g/min in most cerebral regions on theligated side. The greatest reduction of FK binding was noted in the olfactory tubercle, caudate-putamen and globus pallidus, followed by the hippocampus and cerebral cortices. The FK binding tended to be low at lCBF<-20 ml/100g/min in the cerebral cortices, However, the PDBU binding was relatively well preserved in each cerebral structure, and no significant correlation between lCBF and PDBU binding was noted in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult over extensive brain regions, while the PKC system may be relatively resistant to ischemia.
In additional studies, we observed that the AC and PKC systems were stimulated on the ischemic side at 2 hours after ischemia, suggesting that the second-messenger systems may respond to ischemia differently in terms of the phase of ischemia.
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