2000 Fiscal Year Final Research Report Summary
Inducible nitric oxide synthase and neonatal hypoxic-ischemic encephalopathy
Project/Area Number |
11671068
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Embryonic/Neonatal medicine
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Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
HATTORI Haruo Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (80189571)
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Project Period (FY) |
1999 – 2000
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Keywords | neonatal hypoxic-ischemic encephalopathy / nitric oxide / inducible nitric oxide synthase / mRNA |
Research Abstract |
The neuroprotective effect of a selective inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, was evaluated in a neonatal hypoxic-ischemic rat model. We also measured the changes in nitric oxide (NO) metabolites in the brain. Unilateral hypoxic-ischemic injury was produced in the brain of 7-day-old rats by combining a common carotid artery ligation with hypoxic exposure (8% oxygen) for 2.5 h. Histological evaluation of the brain damage was performed 72 h later. Brain NO metabolites were measured by using a NO analyzer at 0 h, 1.5 h (during hypoxia), 2.5 h (end of hypoxia), 6 h, 24 h, and 72 h after the start of hypoxia. Aminoguanidine (300 mg/kg) was injected intraperitoneally nine times at eight-hour intervals starting 1 h before the hypoxia. These selective iNOS inhibitor administrations resulted in 89% reduction of both the cerebral cortical and the striatal infarcted areas compared to those of vehicle injected controls. Repeated injections of aminoguanidine also suppressed the peak of NO metabolites in the brain during the reoxygenation period. These results indicate that NO generated by iNOS during reoxygenation plays a key role in producing neonatal hypoxic-ischemic brain damage. Brain mRNA was measured semiquantitatively at 0 h, 1.5 h (during hypoxia), 2.5 h (end of hypoxia), 6 h, 24 h, 72 h and 96 h after the start of hypoxia. In either hemisphere of the brain, mRNA was detected at 72 h and 96 h after the start of hypoxia. The iNOS inhibitor tended to suppress the emergence of the mRNA.
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Research Products
(3 results)