| Project/Area Number |
09670460
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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 |
Legal medicine
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
TANAKA Noriyuki UOEH・Forensic Medicine, Professor, 医学部, 教授 (60126597)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshiko UOEH・Forensic Medicine, Assistant Professor, 医学部, 講師 (80141745)
KITA Toshiro UOEH・Forensic Medicine, Associate Professor, 医学部, 助教授 (00131912)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Traumatic head injury / Diffuse axonal injury / Tumor necrosis factor-alpha / beta-amyloid precursor protein / Fluid percussion device / Glial cell / MRI |
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| Research Abstract |
We approach to show the immunolocalization of TNF a after diffuse axonal injury (DAI) by midline fluid percussion rat model (moderate brain injury of lOOOmmHg was generated) and the effects of TNF alpha on the axolemmal permeability using horseradish peroxidase as a tracer. Add to this, we investigate the accumulation of beta -amyloid precursor protein (beta -APP), which has recently been shown to be reliable marker for the functional damage of axons associated with fatal head injury. TNF alpha levels of brain tissues, which was impact cortex site including the corpus callosum, gradually increased during the first 1h, rose to a maximal elevation at 3h and gradually decresed at 6h and more decreased to 24h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15min after impact, but rapidly recovered and 1h after impact secondary axonal damage occurred in the corpus callosum nd the brain stem. By the
immunoelectron microscopy, beta -APP accumulated in the axon at 1h after impact and this revealed functional axonal damage. TNF alpha reactions were detected in the lysosomes of microglia at the 3Omin after impact, and 1h after impact these reactions were mainly detected at the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is widely accepted that TNF alpha induces primary demyelination and oligodendrocyte apoptosis. Therefore the delayed axonal damage observed in these sites may be induced by TNF a which is synthesized mainly by glial cells. The present study suggests that TNF alpha conveyed from the glial cells is one cofactor contributing to the DAI formation by the fluid percussive brain injury.
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