Real-time monitoring of intracellular ATP concentration in acute spinal cord injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09527
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: National Cardiovascular Center Research Institute (2021); Osaka University (2019-2020)
• Principal Investigator: Ohnishi Yuichiro 国立研究開発法人国立循環器病研究センター, 研究所, 非常勤研究員 (00533811)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脊髄損傷 / 代謝 / 解糖系 / 軸索変性 / 酸化ストレス / ATP

Outline of Final Research Achievements

Spinal cord injury gradually spreads away from the epicentre of injury. The rate of degeneration on the rostral side of the injury differs from that on the caudal side. The blood flow at the rostral side of the injury showed ischaemia-reperfusion, while the caudal side presented stable perfusion. Although the low-ATP regions expanded at the rostral side of injury until 24h 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 24h 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.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

脊髄損傷後の軸索変性は頭尾側に徐々に広がっていく。損傷頭側での軸索変性は損傷直後から早く進行し、損傷尾側での軸索変性は遅れて進む。損傷頭尾側での軸索変性の進行の違いのメカニズムはよくわかっていない。本研究では脊髄損傷急性期の細胞内ATPのリアルタイムモニタリングを行い、細胞内ATPの時間的空間的変化を明らかにした。そして急性期の脊髄細胞内エネルギー代謝が２次損傷の増悪に与える影響を評価した。また、脊髄損傷の病態を、エネルギー代謝という観点から探索しし、脊髄損傷急性期での軸索変性の進行の違いのメカニズムを世界で初めて明らかにしている。