| Project/Area Number |
15591660
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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 |
MUROZONO Michihiro Tokyo Medical University, Medicine, lecturer, 医学部, 助手 (70276947)
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| Co-Investigator(Kenkyū-buntansha) |
MTSUMOTO Shohei Tokyo Medical University, Medicine, lecturer, 医学部, 講師 (30256250)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | mdrla / knockout mouse / VIP / PACAP / Brain ischemia / mdr1a / 局所脳虚血 / BBB |
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| Research Abstract |
We investigated the functional effects of mdrla encoded P-gp on focal cerebral ischemia, which is prepared by the middle cerebral artery occlusion(MCAO) model, using mdrl a knockout (ko) mice. The ischemic damages were evaluated with measuring and comparing the infarct volumes of mdrla ko mice and wild mice. Infarction volume of mdrla ko mice group was significantly smaller than that seen in wild mice group. The blood pressure and heart rate did not differ between groups. There are no significant differences in PaO_2, PaCO_2, B.E. and hemoglobin before ischemia and 30 min after reperfusion. India ink staining of cerebrovascular anatomy of the circle of Willis demonstrated that there were no gross anatomic differences in the vascular pattern of the cerebral circulation. These results indicate that P-gp leads to exacerbate cerebral infarction in brain ischemia. Next, We examined the effects of IK312548 and Ac-PACAP, which are novel derivatives of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide(PACAP), on brain ischemia induced by two-vessel occlusion(2-VO) and MCAO in mice. IK312548 and Ac-PACAP treatment inhibited neuronal death by 2-VO and MCAO. Concurrently, we examined the neuroprotective effects of ac-PACAP on brain neuronal death induced by glutamate (Glu). The significant inhibitions of ac-PACAP on the cell death unduced by Glu were seen in the neuron/glia cocultured cells. These results indicate that both of them showed the neuroprotection.
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