Humans, primates, and rodents with cervical spinal cord injury (SCI) show permanent sensorimotor dysfunction of the upper/forelimb as consequence of axonal damage and local neuronal death. This work aimed at characterizing a model of cervical SCI in domestic pigs in which hemisection with excision of 1 cm of spinal cord was performed to reproduce the loss of neural tissue observed in human neuropathology. Posture and motor control were assessed over 3 months by scales and kinematics of treadmill locomotion. Histological measurements included lesion length, atrophy of the adjacent spinal cord segments, and neuronal death. In some animals, the retrograde neural tracer aminostilbamidine was injected in segments caudal to the lesion to visualize propriospinal projection neurons. Neuronal loss extended for 4–6 mm from the lesion borders and was more severe in the ipsilateral, caudal spinal cord stump. Axonal Wallerian degeneration was observed caudally and rostrally, associated with marked atrophy of the white matter in the spinal cord segments adjacent to the lesion. The pigs showed chronic monoplegia or severe monoparesis of the foreleg ipsilateral to the lesion, whereas the trunk and the other legs had postural and motor impairments that substantially improved during the first month post-lesion. Adaptations of the walking cycle such as those reported for rats and humans ameliorated the negative impact of focal neurological deficits on locomotor performance. These results provide a baseline of behavior and histology in a porcine model of cervical spinal cord hemisection that can be used for translational research in SCI therapeutics.
Electroactive microfiber-based scaffolds aid neural tissue repair. Carbon microfibers (CMFs) coated with the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] (PEDOT:PSS-co-MA) provide efficient support and guidance to regrowing axons across spinal cord lesions in rodents and pigs. We investigated the electrical and structural performance of PEDOT:PSS-co-MA-coated carbon MFs (PCMFs) for long-term, biphasic electrical stimulation (ES). Chronopotentiometry and electrochemical impedance spectroscopy (EIS) allowed the characterization of charge transfer in PCMFs during ES in vitro, and morphological changes were assessed by scanning electron microscopy (SEM). PCMFs that were 4 mm long withstood two-million-biphasic pulses without reaching cytotoxic voltages, with a 6 mm length producing optimal results. Although EIS and SEM unveiled some polymer deterioration in the 6 mm PCMFs, no significant changes in voltage excursions appeared. For the preliminary testing of the electrical performance of PCMFs in vivo, we used 12 mm long, 20-microfiber assemblies interconnected by metallic microwires. PCMFs-assemblies were implanted in two spinal cord-injured pigs and submitted to ES for 10 days. A cobalt–alloy interconnected assembly showed safe voltages for about 1.5 million-pulses and was electrically functional at 1-month post-implantation, suggesting its suitability for sub-chronic ES, as likely required for spinal cord repair. However, improving polymer adhesion to the carbon substrate is still needed to use PCMFs for prolonged ES.