| Project/Area Number |
01440064
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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 |
麻酔学
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| Research Institution | Yamaguchi University |
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Principal Investigator |
ISHIKAWA Toshizoh (1990) Yamaguchi University, Assistant School of Medicine, 医学部, 助手 (90034991)
武下 浩 (1989) 山口大学, 医学部, 教授 (50034898)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Tomohisa Yamaguchi University Assistant, Hospital, 医学部附属病院, 助手 (10144940)
TATEISHI Akio Yamaguchi University, Assistant Hosipital, 医学部附属病院, 助手 (00155102)
SAKABE Takefumi Yamaguchi University Associate Prof. School of Medicine, 医学部, 助教授 (40035225)
MAEKAWA Tsuyoshi Yamaguchi University, Assochiate Prof. Hospital, 医学部附属病院, 助教授 (60034972)
石川 敏三 山口大学, 医学部, 助手 (90034991)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1990: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1989: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | brain ischemia / ischemic neuronal damage / neurotransmitter / receptor / Ca accumulation / memory disturbance / drug theraphy / microdialysis |
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| Research Abstract |
Recent studies have shown that transient brain ischemia induced delayed neuronal dysfunction, such as an amnesic syndrome secondary to hippocampal neuronal damage in human and rodents. Derangements of neurotransmitter accompanied by elevated intracellular Ca are thought to be one of the major determinant. The present study was designed to gain further insight into the mechanism of delayed neuronal death following ischemia and to exam the therapeutic value of drugs. Wistar rats were anesthetized with N20 and mechanically ventilated. The forebrain ischemia for 10 min was induced by bilateral carotid artery occlusion and hypotension (mBP 50mmHg). Therapeutic drugs were given immediately after start of reperfusion. 1) Neurotransmitter derangement : Following induced ischemia massive release of glutamate (200%) and dopamine (2000%) was occurred and then gradually returned to basal levels within 30 min after reperfusion. Pentobarbital (PB : GABA agonist) or omega-conotxine (Ca blocker) signi
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ficantly inhibited the increase in dopamine release. Decreased specific bindings (in vitro autoradiography) for glutamate (Glu : 3H-glutamate) and mACh (3H-QNB) 7 days following ischemia in rats with nimodipine (NIM) or bifemelane (BIF) were less severe than those in non-treated rat. 2) Ca accumulation : Increased Ca concentrations in hippocampus and cerebral cortex 7 days following ischemia were less severe in rats with NIM, PB and Sadenosyl methionine than those in non-treated rats. 3) Memory and behavioral disturbances : Conditioned avoidance response was disturbed for 7 days following ischemia in non-treated rats while did not change in rats with NIM, PB and BIF. In conclusion, amelioration in memory dysfunction with these drugs was accompanied by aless derangement of neurotransmitter release, recept or binding and intracellular Ca elevation in the vulnerable brain regions. The Ca entry blockers, GABA agonist, NA/ACh activator or accerelation of resynthesis of phosphatidyl choline may be beneficial to prevent delayed neuronal death following brain ischemia. Less
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