| Project/Area Number |
15591633
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MATSUMOTO Mishiya Yamaguchi Univ., School of Medicine, Associate Professor, 医学部, 助教授 (60243664)
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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)
IIDA Yasuhiko Yamaguchi Univ., Hospital, Research Associate, 医学部附属病院, 助手 (90304485)
SAKABE Takefumi Yamaguchi Univ., School of Medicine, Professor, 医学部, 教授 (40035225)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Spinal cord ischemia / Mitochondria / Cyclosporin A / Delayed onset motor dysfunct / Rabbit / 遅発性運動神経障害 / 遅発生運動神経障害 |
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| Research Abstract |
The purpose of the present study was to determine whether mitochondrial dysfunction plays an important role in the mechanism of delayed onset paraplegia after transient spinal cord ischemia. Because cyclosporin A has been reported to preserve mitochondrial integrity in the ischemic condition, we investigated the effects of cyclosporin A on the hind limb motor function and histopathology in rabbits. In our preliminary study, cyclosporin A was found to increase blood glucose concentrations. Therefore, we also investigated an interaction between cyclosporin A and insulin.
At 96 h after reperfusion, all animals without treatments could not jump, whereas all animals treated with cyclosporin A (10 mg/kg/day X 3 days) and insulin (0.3 - 0.4 U/kg) maintained normal hindlimb motor function. Two-thirds of animals treated with insulin only maintained normal hindlimb motor function, whereas all animals treated with cyclosporin A only could not jump. These results suggest that insulin protects against ischemic spinal cord injury and that the combination of cyclosporin A and insulin tends to further improve neurological recovery.
Insulin has been reported to cause both up-regulation of Bcl-XL and down-regulation of Bax, leading to preservation of mitochondrial integrity. Cyclosporin A has been reported to inhibit the activity of calcineurin and to block the mitochondrial permeability transition pore. Therefore, it seems likely that insulin and cyclosporin synergistically protect against ischemic spinal cord injury.
In conclusion, mitochondrial dysfunction may be involved in the development of delayed onset paraplegia after transient spinal cord ischemia.
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