A Novel Rat Model of Venous Hypertensive Myelopathy Produced by Arteriovenous Bypass Plus Venous Stenosis.

ABSTRACT

BACKGROUND AND OBJECTIVES: Venous hypertensive myelopathy (VHM), mainly induced by the spinal dural arteriovenous fistula, is a congestive spinal cord injury that currently has no appropriate animal model available in preclinical research. METHODS: Sprague Dawley rats (280-320 g) were used. The rats were divided into 3 groups (1) Group 1, which underwent renal artery-dorsal spinal venous bypass (AVB group); (2) Group 2, which underwent renal artery-dorsal spinal venous bypass and drainage vein stenosis (AVB/VS group); and (3) Control group, with T13 dorsal vein ligation. The success of the model was assessed using Doppler ultrasound and 7.0-T magnetic resonance imaging. Transmission electron microscopy, histochemistry, proteomics, and western blot analysis were used to evaluate ultrastructural, pathological, and molecular features in the spinal cord and cerebrospinal fluid (CSF). RESULTS: The success rate of the arteriovenous bypass was 100% at 5 days and 83% at 2 weeks. The locomotor assessment showed decreased lower extremity strength in the AVB/VS group (P = .0067), whereas unremarkable changes were found in the AVB and Control groups. Histochemical staining suggested a 2-fold expansion of the dorsal spinal vein in the AVB/VS group, which was lower than that in the AVB group (P < .05); however, the former displayed greater myelin and neuronal damage (P < .05) and slight dilatation of the central canal (P > .05). Proteomics analysis revealed that the complement and coagulation cascade pathways were upregulated in the CSF of AVB/VS rats, whereas the C3 level was elevated both in the CSF and bilateral spinal cord. Furthermore, overexpression of C3, ITGB2, and CD9 in the spinal cord was confirmed by immunoblotting. CONCLUSION: These findings suggest that the AVB/VS model can effectively mimic the clinical and molecular characteristics of VHM. Furthermore, they suggest that impaired deep intramedullary venous drainage is the key reason for the VHM.