2009 Fiscal Year Final Research Report
Investigation of mechanism of developing neonatal hypoxic ischemic encephalopathy establishment of novel therapy.
| Project/Area Number |
20790771
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Osaka City University |
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Principal Investigator |
FUJIOKA Hiroki Osaka City University, 大学院・医学研究科, 登録医 (70382083)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 低酸素虚血 / ビオプテリン / inducible NOS (iNOS) / GTPCH I / NMDA受容体拮抗剤 |
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| Research Abstract |
In this study, we found the expression of inducible nitric oxide synthase (iNOS) in neurons of severe neonatal hypoxic ischemic encephalopathy model piglets after 12 hours. Level of blood biopterin, known as a co-factor of iNOS, was also increased. The increase was inhibited by MK-801, one of NMDA receptor antagonist. However, expression of iNOS was not affected. Guanosine triphosphate cyclohydrolase I (GTPCH) is the rate-limiting enzyme of biopterin synthesis pathway. Previous reports described that proinflammatory cytokines up-regulated the activity of GTPCH. It was suggested that excitatory neurotransmission affected the synthesis of proinflammatory cytokines. On the other hand, rat model of status epilepticus by using kainic acid, an analogue of glutamate, indicated no increase of iNOS in neuron. Those results suggested that the pathways of signal transductions were different between swine and rodents.
Human Segawa Disease was caused by the defect of GTPCH. Generally, biopterin shortage causes hyperphenylalaninemia. However blood phenylalanine concentration of Segawa disease patients was within normal range, for the mutations of GTPCH in Segawa disease were heterozygous. We compared blood phenylalanine levels between patients of Segawa disease and controls. The result was that the blood phenylalanine level in Segawa disease was within normal range however the values were significantly higher than those of controls.
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Research Products
(7 results)
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[Presentation] Japan PND study group NATION-WIDE2010
Author(s)
Haruo Shintaku, Masaya Segawa, Hiroki Fujioka
Organizer
EPIDEMIOLOGIC STUDY OF PEDIATRIC NEUROLOGIC DISEASE IN JAPAN (THE 1ST REPORT) International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD) & The 13th Annual Meeting of the Infantile Seizure Society (ISS)
Place of Presentation
Taipei
Year and Date
20100326-20100328
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