| Project/Area Number |
11470323
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SAKABE Takefumi Yamaguchi Univ., School of Medicine, Professor, 医学部, 教授 (40035225)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Shirou Yamaguchi Univ., Hospital., Research Associate, 医学部・附属病院, 助手 (70322245)
MATSUMOTO Mishiya Yamaguchi Univ., Hospital., Assistant Professor, 医学部・附属病院, 講師 (60243664)
NAKAKIMURA Kazuhiko Yamaguchi Univ., School of Medicine, Assiciate Professor, 医学部, 助教授 (50180261)
KAWATA Ryuuichi Yamaguchi University, Hospital, Research Associate, 医学部, 助手 (20263783)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | spinal cord ischemia / rabbit / necrosis / apoptosis / microglia / astrocyte / macrophage / グリア細胞TUNEL染色 / アガロース電気泳動法 / Nauta染色 / GFAP / RAM-11 / ストレス蛋白 |
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| Research Abstract |
Delayed onset paraplegia is a unique phenomenon that occurs 8 h to 24 h after transient spinal cord ischemia in rabbits. This type of paraplegia was also reported in humans after transient aortic occlusion in thoracoabdominal aneurysm surgery. Therefore, to elucidate the mechanism of delayed onset of paraplegia will give us the strategy to protect the spinal cord against ischemic injury. Using transient (15 min) spinal cord ischemia model in rabbits (15 min), we sought to determine which type of the neuronal death is predominant, apoptosis or necrosis, and to elucidate the role of microglia and macrophage.
To examine the involvement of apoptosis in the delayed onset paraplegia, hindlimb motor function was assessed and the lumbar spinal cord was examined morphologically (HE and TUNEL staining) and biochemically (measurements of the breakdown products of α-fodrin and the patterns of DNA changes of the homogenated spinal cord) at 8, 24, or 48 h after reperfusion. No apoptotic motor neuron
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was found in any animals. There was neither detectable increase in a caspase-3-mediated breakdown product of α-fodrin nor DNA laddering in any animals.
To clarify the role of microglia and macrophage in the delayed onset of paraplegia, the time course of the reactions of microglia, macrophage, and astrocyte was investigated morphologically (at, 2, 4, 8, 12, 24, 48 h after reperfusion). Microglia started to proliferate as early as two hours after reperfusion in all the area of the gray matter irrespective of the severity of neuronal injury. In the animals with severe neuronal injury, the microglial reaction continued to increase and macrophage started to be observed 12 h after reperfusion. Whereas in the animals with slight neuronal injury, this early activation began to subside at 24 h and no macrophage was found until 48 h after reperfusion. Although astroglial reaction also occurred as early as two hours after reperfusion, its hypertrophy and hyperplasia were observed in the case of severe neuronal injury.
The results suggest that the delayed onset paraplegia is not associated with apoptotic motor neuron death but with necrotic cell death. There is no evidence that the reactions of microglia, macrophage, and astrocyte after transient ischemia is cytotoxic to motor neurons. These glial cells and macrophages appear to play a role in preventing the extension of ischemic damage. Less
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