The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.
Recent demographics demonstrate an increase in the number of elderly spinal cord injury patients, motivating the desire for a better understanding of age effects on injury susceptibility. Knowing that age and disease affect neurological tissue, there is a need to better understand the sensitivity of spinal cord injury mechanics to variations in tissue behavior. To address this issue, a plane-strain, geometrically nonlinear, finite element model of a section of a generic human thoracic spinal cord was constructed to model the response to dorsal compression. The material models and stiffness responses for the grey and white matter and pia mater were varied across a range of reported values to observe the sensitivity of model outcomes to the assigned properties. Outcome measures were evaluated for percent change in magnitude and alterations in spatial distribution. In general, principal stresses (114-244% change) and pressure (75-119% change) were the outcomes most sensitive to material variation. Strain outcome measures were less sensitive (7-27% change) than stresses (74-244% change) to variations in material tangent modulus. The pia mater characteristics had limited (<4% change) effects on outcomes. Using linear elastic models to represent non-linear behavior had variable effects on outcome measures, and resulted in highly concentrated areas of elevated stresses and strains. Pressure measurements in both the grey and white matter were particularly sensitive to white matter properties, suggesting that degenerative changes in white matter may influence perfusion in a compressed spinal cord. Our results suggest that the mechanics of spinal cord compression are likely to be affected by changes in tissue resulting from aging and disease, indicating a need to study the biomechanical aspects of spinal cord injury in these specific populations.
Previous work suggests females are evolutionarily adapted to have greater lumbar lordosis than males to aid in pregnancy load-bearing, but no consensus exists. To explore further sex-differences in the lumbar spine, and to understand contradictions in the literature, we conducted a cross-sectional retrospective study of sex-differences in lumbar spine morphology and sacral orientation. In addition, our sample includes data for separate standing and supine samples of males and females to examine potential sex-differences in postural loading on lumbosacral morphology. We measured sagittal lumbosacral morphology on 200 radiographs. Measurements include: lumbar angle (L1-S1), lumbar vertebral body and disc wedging angles, sacral slope and pelvic incidence. Lumbar angle, representative of lordotic curvature between L1 and S1, was 7.3° greater in females than males, when standing. There were no significant sex-differences in lumbar angle when supine. This difference in standing lumbar angle can be explained by greater lordotic wedging of the lumbar vertebrae (L1-L5) in females. Additionally, sacral slope was greater in females than males, when standing. There were no significant sex-differences in pelvic incidence. Our results support that females have greater lumbar lordosis than males when standing, but not when supine - suggesting a potentially greater range of motion in the female spine. Furthermore, sex-differences in the lumbar spine appear to be supported by postural differences in sacral-orientation and morphological differences in the vertebral body wedging. A better understanding of sex-differences in lumbosacral morphology may explain sex-differences in spinal conditions, as well as promote necessary sex-specific treatments.
The rostral-caudally aligned fiber-reinforced structure of spinal cord white matter (WM) gives rise to transverse isotropy in the material. Stress and strain patterns generated in the spinal cord parenchyma following spinal cord injury (SCI) are multidirectional and dependent on the mechanism of the injury. Our objective was to develop a WM constitutive model that captures the material transverse isotropy under dynamic loading. The WM mechanical behavior was extracted from the published tensile and compressive experiments. Combinations of isotropic and fiber-reinforcing models were examined in a conditional quasi-linear viscoelastic (QLV) formulation to capture the WM mechanical behavior. The effect of WM transverse isotropy on SCI model outcomes was evaluated by simulating a nonhuman primate (NHP) contusion injury experiment. A second-order reduced polynomial hyperelastic energy potential conditionally combined with a quadratic reinforcing function in a four-term Prony series QLV model best captured the WM mechanical behavior (0.89 < R2 < 0.99). WM isotropic and transversely isotropic material models combined with discrete modeling of the pia mater resulted in peak impact forces that matched the experimental outcomes. The transversely isotropic WM with discrete pia mater resulted in maximum principal strain (MPS) distributions which effectively captured the combination of ipsilateral peripheral WM sparing, ipsilateral injury and contralateral sparing, and the rostral/caudal spread of damage observed in in vivo injuries. The results suggest that the WM transverse isotropy could have an important role in correlating tissue damage with mechanical measures and explaining the directional sensitivity of the spinal cord to injury.
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