Rostro-caudal different energy metabolism leading to differences in degeneration in spinal cord injury

Brain Commun. 2021 Mar 28;3(2):fcab058. doi: 10.1093/braincomms/fcab058. eCollection 2021.


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. 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 ischaemia-reperfusion, while the caudal side presented stable perfusion. The rostral side had an ATP shortage 20 min 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.

Keywords: ATP; degeneration; glycolysis; metabolism; oxidative stress.