Establishment And Evaluation Of Spinal Cord Venous Hypertension In Animal Model

Objectives: To establish the animal model of spinal cord venous hypertension with high reliability and reproducibility. This study was undertaken to explore the temporal manifestations of rabbit spinal cord venous hypertension induced by operative maneuver on MRI imaging and histological examination.Methods: 22 New Zealand albino rabbit were recruited: 18 for model group and 4 for control group. Side-end anastomosis between left renal artery and vein was performed to establish the complications of spinal cord venous hypertension. We ligated the distal end of left renal artery and vein, proximal end of the inferior vena cava above the level of both renal veins as well as its distal end at the level of the descendant colon vein, in order to make the arterial blood stream in left renal artery reverse back to inferior vena cava via arterio-venous fistulae and then drainage to paraspinal venous plexus, resulting in spinal cord venous hypertension. Sham operation were performed in control group (n=4) without arterio-venous fistula establishment. Two were incised on abdomen, with left renal artery and vein exposed (same procedure period as in the model group). Another two were included as normal control. Post-operative models were divided into three groups, acute (<3 days), sub-acute (3 day 3 weeks) and chronic (time>3 weeks). Neurological evaluations were performed at 1st day, 3rd day, 1st week, and 2nd week and so on, respectively. Two were randomly drawn from each group to examine the patency of fistulae; subsequent MRI examination was performed to observe the imaging manifestations; after the sacrifice of the animals, the full spinal cord specimen was removed for macroscopic and pathological examinations (spinal cord neuron, capillary and demyelination under light microscopy).Results: Of the 18 animals in model group, 13 survived and 5 died. The animal in control group all survived. Patency of AVF was shown in 3 animals by DSA (2 in sub-acute and 1 in acute group). Occlusion of AVF was shown in 3 animals (1 in sub-acute and 2 in chronic group). Hypokenesia and hypoesthesia of both hindlegs was observed at different stages. Edema-like imaging of the spinal cord was observed as high-intensity signal on MRI T₂WI sequence, particularly for those located thorax and lumber segment. Gross examination found the swelling of the spinal cord, and microscopic evidence showed the degeneration, apoptosis of the spinal cord neurons, capillary dilation, and neuroglia demyelination. Conclusion: an elaborate animal model of rabbit spinal cord venous hypertension was established with great reliability and reproducibility, which could be used to mimic spinal cord vascular malformation for future study although some improvement might be wananted.