| Project/Area Number |
16591056
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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 |
Pediatrics
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
KAWASHIMA Hisashi Tokyo Medical University, Medicine, Lecturer, 医学部, 講師 (70224772)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEKUMA Kouji Tokyo Medical University, Medicine, Assistant Professor, 医学部, 助教授 (80246173)
KASHIWAGI Yasuyo Tokyo Medical University, Medicine, Lecturer, 医学部, 講師 (00287129)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | influenza-associated encephalopahty / astrocyte / NOx / IL-6 / glia cell / nitrotyrosine / apoptosis / 亜鉛 / グルタミン酸 |
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| Research Abstract |
The number of patients with a new type of influenza-associated encephalopathy and influenza-associated sudden death in children is increasing in Japan on a nationwide scale. The actual pathophysiology is not known, because the virus could not be detected in the central nervous system (CNS) of affected patients. We found that NOx levels and D-ROM in serum and cerebrospinal fluid (CSF) obtained from patients with influenza-associated encephalopathy were high and also reported that extraordinary increases of excitatory amino acid levels in CSF were found in those patients. The NWS virus infected mice body weights were significantly reduced at day 6 p.i. and the virus was obviously detected in the brain on day 1 p.i. The amount of iNOS mRNA in the infected mouse brain was greater than control mouse in each brain region, particularly olfactory bulb and hippocampus on day 1p.i. As for olfactory bulb, the hippocampus iNOS mRNA expression was markedly detected on day 3, and 6 p.i. as well. There was a marked increase of metabolites of nitric oxide in the olfactory bulb and hippocampus. As for immunohistichemistry, positive staining of iNOS was detected mostly in the hippocampus of infected mouse brain. Moreover, both anti-iNOS and GFAP stains were positive mostly around the capillary blood vessels of the hippocampus from an initial stage. These results indicate that NWS virus can invade the brain through the olfactory pathways and then enhance the astrocytes and iNOS which activate the NO production and the expansion of capillary blood vessels. Thus these activations may cause the severe influenza-associated encephalopathy.
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