| Project/Area Number |
14571587
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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 |
Obstetrics and gynecology
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| Research Institution | Nihon University |
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Principal Investigator |
MASAOKA Naoki Nihon University, School of Medicine, assistant professor, 医学部, 講師 (50199668)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAISHI Masaji Nihon University, School of Medicine, assistant professor, 医学部, 講師 (70297810)
HAYAKAWA Yasuhito Nihon University, School of Medicine, Leccturer, 医学部, 助手 (10350018)
大亀 幸子 日本大学, 医学部, 助手 (90318402)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | fetal brain damage / umbilical cord / hypoxia-ischemia-reperfusion / oxygen free radical / antioxidant / free radical scavenger / 臍帯血流障害 / 虚血・低酸素-再灌流 / フリーラジカル / HCI-186 / MCH-186 / 虚血性・低酸素-再還流 / キサンチンオキシダーゼ / アロプリノール |
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| Research Abstract |
As the cause of fetal brain damage we paid attention to the umbilical cord problem during pregnancy and delivery. In other words, a spontaneous cord complication might cause a transient fetal hypoxia-ischemia episode that, although not severe enough to result in death, is significant enough to irreversibly damage critical areas of the developing brain.
Using chronic instrumented fetal lamb, we demonstrated that a large quantity of superoxide resulted from increased conversion of hypoxanthine to xanthine generated in the fetal brain white matter without causing a remarkable degree of acidosis in the fetus during intermittent umbilical cord occlusion and production of hydroxyl radical during and after persistent 10 minutes umbilical cord occlusion. Based on these results we administered allopurinol acting as xanthine oxidase inhibitor to maternal circulation during intermittent umbilical cord occlusion and demonstrated the complete suppression of superoxide production in the fetal brain. Furthermore we also demonstrated that administration of MCI-186 (3-metyl-phenyl-2-pyrazolin-5-one : Edaravone), powerful antioxidative radical scavenger and only drug currently available in clinical practice for the treatment of cerebral infarction, into the maternal circulation reduced hydroxyl radical production induced by 10 minutes persistent umbilical cord occlusion in the fetal lamb brain and confirmed preventive effect on fetal brain damage pathologically.
Although morphologic difference exist between the placenta in human and sheep, our results demonstrated good transfer of allopurinol and MCI-186 from mother to fetus and adequate inhibition of oxygen free radicals production in the fetal brain and suggest the possibility of intrauterine management to reduce fetal brain damage caused by oxygen free radical synthesized by umbilical cord compression during pregnancy and/or delivery.
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