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There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.

Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). Kinematic parameters, including limb coordination and proximal and distal limb angles, were measured. Findings indicate that YMPs use a lateral sequence footfall pattern across all speeds. Stride and stance durations decreased with increasing speed whereas swing duration showed no significant change. Across all speeds assessed, no significant differences were noted between hindlimb stepping parameters for bipedal or quadrupedal gait with the exception of distal limb angular kinematics. Specifically, significant differences were observed between locomotor tasks during maximum flexion (quadrupedal > bipedal), total excursion (bipedal > quadrupedal), and the phase relationship between the timing of maximum extension between the right and left hindlimbs (bipedal > quadrupedal). Speed also impacted maximum flexion and right-left phase relationships given that significant differences were found between the fastest speed (3.5 km/h) relative to each of the other speeds. This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.

Transfer of information across a spinal lesion is required for many aspects of recovery across diverse motor systems. Our understanding of axonal plasticity and which subpopulations of neurons may contribute to bridging substrates following injury, however, remains relatively incomplete. Most recently, attention has been directed to propriospinal neurons (PSNs), with research suggesting that they are capable of bridging a spinal lesion in rodents. In the current study, subpopulations of both long (C5) and short (T6, T8) PSNs-as well as a supraspinal system, the rubrospinal tract (RST)-were assessed following low thoracic (T9) hemisection in the cat using the retrograde tracer Fluoro-Gold. Acutely, within 2 weeks post-hemisection, the numbers of short and long PSNs, as well as contralateral RST neurons, with axons crossing the lesion were significantly decreased relative to uninjured controls. This decrease persisted bilaterally and was permanent in the long PSNs and the contralateral red nucleus (RN). However, by 16 weeks post-hemisection, the numbers of ipsilesional and contralesional short PSNs bridging the lesion were significantly increased. Further, the number of contralesional contributing short PSNs was significantly greater in injured animals than in uninjured animals. A significant increase over uninjured numbers also was seen in the ipsilateral (non-axotomized) RN. These findings suggest that a novel substrate of undamaged axons, which normally terminates rostral to the lesion, grows past a thoracic lesion after injury. This rostral population represents a major component of the bridging substrate seen and may represent an important anatomical target for evolving rehabilitation approaches as a substrate capable of contributing to functional recovery.

Following a lateralized spinal cord injury (SCI) in humans, substantial walking recovery occurs; however, deficits persist in adaptive features of locomotion critical for community ambulation, including obstacle negotiation. Normal obstacle negotiation is accomplished by an increase in flexion during swing. If an object is unanticipated or supraspinal input is absent, obstacle negotiation may involve the spinally organized stumbling corrective response. How these voluntary and reflex components are affected following partial SCI is not well studied. This study is the first to characterize recovery of obstacle negotiation following low-thoracic spinal hemisection in the cat. Cats were trained pre- and post-injury to cross a runway with an obstacle. Assessments focused on the hindlimb ipsilateral to the lesion. Pre-injury, cats efficiently cleared an obstacle by increasing knee flexion during swing. Post-injury, obstacle clearance permanently changed. At 2 weeks, when basic overground walking ability been recovered, the hindlimb was dragged over the obstacle (∼90%). Surprisingly, the stumbling corrective response was not elicited until after 2 weeks. Despite a notable increase, between 4 and 8 weeks, in the ability to modify limb trajectory when approaching an obstacle, limb lift during obstacle approach was insufficient during ∼50% of encounters and continued to evoke the stumbling corrective response even at 16 weeks. A post-injury lead limb bias identified during negotiations with complete clearance, suggests a potential training strategy to increase the number of successful clearances. Therefore, following complete severing of half of the spinal cord, the ability to modify ipsilateral hindlimb trajectory shows significant recovery and by 16 weeks permits effective clearing of an obstacle, without contact, ∼50% of the time. Although this suggests plasticity of supporting circuitry, it is insufficient to support consistent clearance. This inconsistency, even at the most chronic time point assessed (16 weeks), is probably a contributing factor to falls reported for people with SCI.