Dichotomous Locomotor Recoveries Are Predicted by Acute Changes in Segmental Blood Flow after Thoracic Spinal Contusion Injuries in Pigs.

Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.

Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation.

Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model.