| Project/Area Number |
17300190
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Rehabilitation science/Welfare engineering
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| Research Institution | Research Institute, National Rehabilitation Center for Persons with Disabilities (2005, 2007)
The University of Tokyo (2006) |
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Principal Investigator |
OGATA Toru Research Institute, National Rehabilitation Center for Persons with Disabilities, Department of Rehabilitation for Movement Functions, Research Institute, Chief Researcher (00392192)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHIKAWA Shinya NATIONAL REHABILITATION CENTER, Department of Rehabilitation for Movement Functions, Research Institute, National Rehabilitation Center, Researcher (60455376)
AKAI Masami NATIONAL REHABILITATION CENTER, Department of Rehabilitation for Movement Functions, Research Institute, National Rehabilitation Center, Director (80143452)
山本 真一 国立身体障害者リハビリテーションセンター研究所, 運動機能系障害研究部, 主任研究官 (30282560)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,760,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥960,000)
Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2006: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | spinal cord injury / apoptosis / intracellular signaling pathways / glia cell / gene transfer / オリゴデンドロサイト / 前駆細胞 / 細胞死 |
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| Research Abstract |
This project aims innovation of a new therapeutic approach for spinal cord injury and we focused on oligodendrocytes, one of glial cell types, and their cell death. For the first year, we analyzed immuno-histochemical specimen taken from rat spinal cord injury model and we found that many oligodendrocytes die when they are in the progenitor state as well as in the mature state. We consider the cell death of oligodendrocyte progenitor cells (OPCs) is more important from the view point of tissue repair, therefore we looked into the cell function of OPCs.
For the second year, we use in vitro culture experiment to identify the factors which induce OPC cell death. Several inflammatory cytokines are screened for their capacity to induce OPC cell death. As the results, interferon-gamma (IFNg) was found to be most potent to induce apoptotic cell death in OPC population. The expression of IFNg was confirmed in mice spinal cord injury model and, interestingly, the period of IFNg expression was co
… More
incide with the period when OPCs fell into cell death in injured spinal cord.
For the final year, we further analyzed the effect of IFNg singals in in vivo. Since viral mediated gene transfer was not successful, we utilized IFNg receptor deficient mice to analyze the blockade effects of IFNg signals to the survival of OPCs in injured spinal cord. As the results, OPCs cell death was significantly reduced in IFNg receptor deficient mice following spinal cord injury. In addition to it, the motor function of the lower limbs was improved in the mutant mice. Therefore, the preservation of OPCs in injured spinal cord seemed to contribute to the functional recovery after spinal cord injury.
Those results of this project imply two points. First, the result shows that the preservation of OPCs in injured spinal cord could be a candidate for therapeutic target of traumatic injury in central nervous systems. Secondly, interfering IFNg signals was proven to be a new way of immuno-modulation therapy for spinal cord injury. Less
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