Developing preclinical dog models for reconstructive severed spinal cord continuity via spinal cord fusion technique

Abstract

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model.

Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery.

Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery.

Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Keywords: Polyethylene glycol; Spinal cord fusion; Spinal cord injury; Spinal cord transplantation; Surgical procedure.

Fig. 1

cBBB scores. The cBBB scores in the SCT, vSCT, and vASCT surgical models at different time points. The recovery of motor function in the three groups showed an upward trend over time. Significant differences in cBBB scores were observed among the SCT, vSCT, and vASCT surgical models at 3, 10, 17 and 24-day post-operation (p<0.05), while no significant differences in cBBB scores were revealed among the SCT, vSCT, and vASCT surgical models at 31, 38, 45, 52, 59 and 180-day post-operation (p>0.05).

Fig. 2

T2W and DTI at 6-month post-operation. T2-weighted MRI scans indicated increased re-establishment of anatomic tissue continuity across the graft site in SCT-treated (A), vSCT-treated (C) and vASCT-treated (E) dogs. DTI showed continued fiber regrowth across the transection plane in the SCT (B), vSCT (D) and vASCT (F) surgical models.

Fig. 3

MEP examination in the SCT, vSCT, and vASCT surgical models. Positive MEP waveforms were recorded in all three groups after operation, but the latency and amplitude were prolonged and lower to varying degrees compared with those before operation.