Correlations between tissue-level stresses and strains and cellular damage within the guinea pig spinal cord white matter

Strain magnitude, strain rate, axon location, axon size, and the local tissue stress state have been proposed as the mechanisms governing primary cellular damage within the spinal cord parenchyma during slow compression injury. However, the mechanism of axon injury has yet to be fully elucidated. The objective of this study was to correlate cellular damage within the guinea pig spinal cord white matter, quantified by a horseradish peroxidase (HRP) exclusion test, with tissue-level stresses and strains using a combined experimental and computational approach. Force–deformation curves were acquired by transversely compressing strips of guinea pig spinal cord white matter at a quasi-static rate. Hyperelastic material parameters, derived from a Mooney–Rivlin constitutive law, were varied within a nonlinear, plane strain finite element model of the white matter strips until the computational force–deformation curve converged to the experimental results. In addition, white matter strips were subjected to nominal compression levels of 25%, 50%, 70%, and 90% to assess axonal damage by quantifying HRP uptake. HRP uptake density increased with tissue depth and with increased nominal compression. Using linear and nonlinear regression analyses, the strongest correlations with HRP uptake density were found for groups of tissue-level stresses and groups of log-transformed tissue-level strains.