| Project/Area Number |
09671718
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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 SCHOOL OF MEDICINE |
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Principal Investigator |
MASAOKA Naoki ASSISTANT PROFESSOR, 医学部, 講師 (50199668)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAISHI Masazi LECTURER, 医学部, 助手 (70297810)
TAKAGI Kenjiro ASSISTANT PROFESSOR, 医学部, 講師 (00216623)
MIYAKE Yosiaki ASSOCIATE PROFESSOR, 医学部, 助教授 (20183634)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | FETAL BRAIN DAMAGE / UMBILICAL CIRCULATION / UTERINE ARTERY / FREE RADICALS / EXCITATORY AMINO ACIDS / APOPTOSIS / FREE RADICAL SCAVENGERS / ALLOPURINOL / Fas-L) / 胎児 / 脳神経障害 / NMDA受容体 / APP染色 / NMDAレセプター / NO / アポトーシス / サイトカイン |
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| Research Abstract |
The purpose of this project was demonstrating the mechanisms of fetal brain damage before labor and onsiderating the preventive management. As the insult that is not severe enough to result in death, is significant enough to irreversibly damage in the developing brain, we evaluated intermittent partial occlusion of umbilical circulation and transient interruption of uterine and ovarian arteries. We thought these were hypoxia-ischemia-reperfusion models. (1) Using chronically instrumented fetal lambs investigations were made by occluding umbilical circulation for 1 of every 3 minutes for 2 hours. As the result, there was no change in PCO_2 and pH without slightly decrease of PO_2 of about 3mmHg. However, in fetal brain extracted 3 days after the experiment, the appearance of apoptotic cells was confirmed at periventricular region, basal ganglia and hippocampus of fetal brain. In addition, we recognized the release of large amounts of oxygen free radicals resulting from increased conversion of hypoxanthine to xanthine, mildly increase of glutamate and significant decrease of GABA.(2) By interruption of uterine and ovarian arteries in pregnant rats for 20 minutes followerd by restoration of circulation. We observed the same pathlogical changes in fetal brainn Furthermore, we found the increase Fas/FasL, IL-1 α, β, IL-8, TNF-α and INF-γ. (3) We evaluated the possibility of allopurinol, a classic drug for gout, that acts as xanthine oxidase inhibitor and free radical scavengers. We could demonstrate a good transfer of allopurinol from mother to fetus without obvious side effects and complete suppression of production of oxygen free radicals during intermittent partial umbilical cord occlusion. This result suggested the possibility of intrauterine treatment to prevent fetal brain damage.
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