| Project/Area Number |
12671503
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
MATSUMOTO Shohei Tokyo Medical University, Medicine, lecuturer, 医学部, 講師 (30256250)
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| Co-Investigator(Kenkyū-buntansha) |
ISSHIKI Atsushi Tokyo Medical University Medicinem professor, 医学部, 教授 (60074796)
MUROZANO Michihiro Tokyo Medical University Medicinem, research assistant, 医学部, 助手 (70276947)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | mdrla knockoutmice / Cyclosporin A / Cytochrome C / cerebral ischemia / mitochondrial Permeability / Transition Pore / Mitochondrial Permeability Transition Pore / mdr1aノックアウトマウス / Mitochondrial Permeability Transition Pore (6) |
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| Research Abstract |
We investigated the efficacy of cyclosporin A (CsA) for brain ischemia using focal ischemic model of mdrla knockout (KO) mice which lacks p-glycoprotein resulting CsA easily pass through blood brain bomer (BBB). At first, we made focal ischemic model of FVB mice (wild type of mdria knockout mice), then 10mg/kg CsA administered during reperfusion, diminishes infarct size in the model. This result is the first evidence of CsA's neuroprotective effect in mice brain ischemia. In mdrla KO mice, we demonstrate 2mg/kg and even 1mg/kg CsA significantly reduce infarct size when administered after reperfusion. These results suggest that CsA has potent neuroprotective effect, if it reaches brain parenchyma. Interestingly, 10mg/kg CsA administration is not effective in focal ischemic model of mdrla KO mice. 10mg/kg CsA may be too much for mdala KO mice because CsA concentration in the brain is possibly unusually high. The mechanism whereby CsA is protective in ischemia-reperfusion damage is however equivocal. Using our CsA model of mdria KO mice, cytosolic cytochrome C in the brain was analyzed by Western blot during reperfusion. Cytosolic cytochrome C in CsA 1mg/kg administrated KO mice brain was lower than that of vehicle administrated mice. This result suggests that CsA prevents mitochondrial permeability transition pore opening, and release of cytochrome C from the pore.
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