Humans, primates, and rodents with cervical spinal cord injury (SCI) show permanent sensorimotor dysfunction of the upper/fore limb 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 one centimeter 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 to 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 postlesion. Adaptations of the walking cycle like 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.

The anatomy of the cortical motor system and its relationship to motor repertoire in artiodactyls is for the most part unknown. We studied the origin and termination of the corticospinal tract (CST) and cortico-brainstem projections in domestic pigs. Pyramidal neurons were retrogradely labeled by injecting aminostilbamidine in the spinal segment C1. After identifying the dual origin of the porcine CST in the primary motor cortex (M1) and premotor cortex (PM), the axons descending from those regions to the spinal cord and brainstem were anterogradely labeled by unilateral injections of dextran alexa-594 in M1 and dextran alexa-488 in PM. Numerous corticospinal projections from M1 and PM were detected up to T6 spinal segment and showed a similar pattern of decussation and distribution in the white matter funiculi and the gray matter laminae. They terminated mostly on dendrites of the lateral intermediate laminae and the internal basilar nucleus, and some innervated the ventromedial laminae, but were essentially absent in lateral laminae IX. Corticofugal axons terminated predominantly ipsilaterally in the midbrain and bilaterally in the medulla oblongata. Most corticorubral projections arose from M1, whereas the mesencephalic reticular formation, superior colliculus, lateral reticular nucleus, gigantocellular reticular nucleus, and raphe received abundant axonal contacts from both M1 and PM. Our data suggest that the porcine cortical motor system has some common features with that of primates and humans and may control posture and movement through parallel motor descending pathways. However, less cortical regions project to the spinal cord in pigs, and the CST neither seems to reach the lumbar enlargement nor to have a significant direct innervation of cervical, foreleg motoneurons.

Our results suggest that the activation of CB2 receptors could be considered a useful therapeutic approach for Alzheimer's disease.