Background

A clinically relevant mouse model of thoracic endovascular aortic repair-induced ischemic spinal cord injury has been lacking since the procedure was first employed in 1991. We hypothesized that ligation of mouse intercostal arteries would simulate thoracic endovascular aortic repair-induced ischemic spinal cord injury and behavioral deficit. We aimed to create a mouse model of thoracic endovascular aortic repair-induced spinal cord hypoperfusion by ligating five pairs of mouse intercostal vessels.

Methods

Mice were divided into sham (n=53) and ligation (n=60) groups. We double ligated three pairs and single ligated two pairs of thoracic intercostal arteries in adult C57BL/6 mice. A laser doppler probe was used in vivo on the spinal cords and intercostal arteries to document the extent of arterial ligation and spinal cord hypoperfusion. The Basso Mouse Scale for Locomotion, histological studies, and electron microscopy demonstrated post-ligation locomotive and histopathological changes.

Results

Ligation induced a significant and instantaneous drop in blood flow in the intercostal arteries (% change) (mean=-63.81, 95%CI: -72.28 to -55.34) and the thoracic spinal cord (% change) (mean=-68.55, 95%CI: -80.23 to -56.87).

Paralysis onset was immediate and of varying degree, with behavioral deficit stratified into three groups: 9.4% exhibited severe paralysis, 37.5% moderate paralysis, and 53.1% mild paralysis at day 1 (n=32; p<0.001). Mild and moderate paralysis was transient, gradually improving over time. Severe paralysis showed no improvement and exhibited a higher mortality rate (83%; n=15/18) compared to moderately (33%; n=6/18) and mildly (24%; n=6/25) paralyzed mice (p<0.001). The overall ligation group survival rate (84%; n=46/55) was significantly lower than the sham group (100%; n=48/48) with p=0.003.

Conclusion

Our mouse model generates reproducible spinal cord hypoperfusion and accompanying histopathological ischemic spinal cord damage. The resulting anatomical changes and variable behavioral deficits mimic the variability in radiological and clinical findings in human patients.