2020 Fiscal Year Research-status Report
Real-time monitoring of intracellular ATP concentration in acute spinal cord injury
| Project/Area Number |
19K09527
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| Research Institution | Osaka University |
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Principal Investigator |
大西 諭一郎 大阪大学, 医学系研究科, 助教 (00533811)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ATP / metabolism / spinal cord injury / degeneration / glycolysis / oxidative stress |
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| Outline of Annual Research Achievements |
Spinal cord injury gradually spreads away from the epicenter of injury. The rate of degeneration on the rostral side of the injury differs from that on the caudal side. Rostral degeneration is an immediate process, while caudal degeneration is delayed. In this study, we demonstrated that the rostro-caudal differences in energy metabolism led to differences in the spread of degeneration in early thoracic cord injury using in vivo imaging. The blood flow at the rostral side of the injury showed ischemia-reperfusion, while the caudal side presented stable perfusion. The rostral side had an ATP shortage 20 minutes after spinal cord injury, while the ATP levels were maintained on the caudal side. Breakdown products of purine nucleotides were accumulated at both sides of injury 18 h after spinal cord injury, but the principal metabolites in the tricarboxylic acid cycle and glycolytic pathway were elevated on the caudal side. Although the low-ATP regions expanded at the rostral side of injury until 24 h after spinal cord injury, the caudal-side ATP levels were preserved. The low-ATP regions on the rostral side showed mitochondrial reactive oxygen species production. Administration of 2-deoxy-D-glucose as a glycolysis inhibitor decreased the caudal ATP levels and expanded the low-ATP regions to the caudal side until 24 h after spinal cord injury. These results suggest that deficits in the glycolytic pathway accelerate the caudal degeneration, while immediate rostral degeneration is exacerbated by oxidative stress in early thoracic cord injury.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
予定していた実験が終了し、新たな知見が得られた。既存の結果に関しては論文化している。
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| Strategy for Future Research Activity |
急性期の新たな治療戦略となる薬剤や治療タイミングを調べている。
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| Causes of Carryover |
論文化した費用の請求が次年度に繰り越されたことや、既存の機器を再利用して実験を行えたことが差額の出現につながった。
急性期の新たな治療戦略となる薬剤や治療タイミングを調べる。
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