| Project/Area Number |
11680757
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Kagawa Medical University |
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Principal Investigator |
MIYAMOTO Osamu Kagawa Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00253287)
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| Co-Investigator(Kenkyū-buntansha) |
ITANO Toshifumi Kagawa Medical University, Faculty of Medicine, Professor, 医学部, 教授 (60145042)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Hypothermia / Cerebral ischemia / Apoptosis / MK-801 / NMDA recepor / Combination therapy / Hippocampus / Neuronal cell death / グルタミン酸受容体 / 砂ネズミ / 前脳虚血 / AMPA受容体 / RT-PCR / 長期増強 / 8方向迷路 / 慢性的な細胞死 |
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| Research Abstract |
The long-term effects of post-ischemic hypothermia on neuronal survival were investigated using global ischemia in gerbils. Hypothermia was induced at 32 ℃ x 4hr immediately after ischemia. Morphological, biological, and functional examinations were performed at 1 week and 1 month after ischemia. Post-ischemic hypothermia prevented ischemic cell death at 1 week, however, the degree of protective effect of post-ischemic hypothermia was reduced at 1 month after ischemia. Some neurons were dead with DNA fragmentation after hypothermia. Both immunohistochemistry and in situ hybridization showed abnormality of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus, and long-term potentiation was also depressed at 1 week after ischemia. The administration of MK-801, which is a non-competitive NMDAR antagonist, prevented the chronic cell death after post-ischemic hypothermia. The performance of eight-arm radical trial in gerbils was well maintained at 1 month after ischemia by the hypothermia with MK-801 treatment, but not only hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the chronic cell death. Some neurons were dead associated with apoptosis. The combination of post-ischemic hypothermia and administration of MK-801 is useful for neuronal protection against ischemic insult.
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