| Project/Area Number |
12470288
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | 山梨医科大学 |
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Principal Investigator |
NUKUI Hideaki University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (20008303)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIZUME Kazuhiro University of Yamanashi, Faculty of Medicine, Research Associate, 医学部, 助手 (00260571)
SUGITA Masao University of Yamanashi, Faculty of Medicine, Research Associate, 医学部, 助手 (70235886)
大橋 康弘 山梨医科大学, 医学部, 医員
宮沢 伸彦 山梨医科大学, 医学部, 講師 (60209898)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | cerebral infarction / repetitive ischemia / glutamate / exite-toxity / microdialysis / mGluR agonist / ischemic tolerance / rat model / micro dialysis / preconditioning / mGluR / cerebral blood flow / heat shock protein / reperfusion injury / endothelium |
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| Research Abstract |
Background and purpose: Recent progress in neuroscientific research revealed delayed neuronal death and ischemic tolerance after sublethal ischemia. The purpose of this study is to investigate the influence of the repetitive short time ischemia on the cerebral circulation and metabolism of the brain. Method: Using the rat focal ischemia model (Koizumis model), middle cerebral artery was occluded 5 min. and reperfused 10 min. by inserting and removing the intraluminal thread for three times. We collected the data to evaluate following issues. 1) Cerebral blood flow change at reperfusion by Laser Doppler flowmetry. 2) Induction of the heat shock protein 70 (hsp-70) by Western blot. 3) Glutamate release by ischemia in both acute and chronic state and 4) the effect on glutamate release by metabolic glutamate receptor agonist, DCG-IV, by means of microdialysis technique. Result: 1) Diminution of the reactive hyperemia by increasing time of occlusion. 2) The induction of hsp-70 was not specific for the ischemia time or times of repetition. 3) There was no evidence of cumulative effect of glutamate by repeated ischemic insults. In the chronic stage, four weeks after repetitive ischemia, the release of glutamate was not elicited by prolonged ischemic event. 4) DCG-IV tended to attenuated the glutamate release. Discussion: Repeated insertion of intraluminal thread caused vascular damage, therefore more than half of the animals suffered from subarachnoid hemorrhage or permanent occlusion and excluded from evaluation. Inconsistency of the hsp-70 induction is speculated to be due to the inconsistency of the severalty and extent of the ischemia caused by the intraluminal thread insertion. The attenuation of glutamate release in a chronic stage after repeated short duration ischemia has not been reported. Continuing research to elucidate the mechanism of these novel findings is important.
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