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

https://doi.org/10.1016/j.jbiomech.2007.03.014Get rights and content

Abstract

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.

Introduction

Slow compression spinal cord injuries result from degenerative, infective, or oncologic lesion growths within the spinal canal; the narrowed spinal canal exerts pressure throughout the entire spinal cord parenchyma, resulting in white matter cellular damage. Neurological deficits appear when the spinal cord cross-sectional area is reduced by 30% and are irreversible when cord area reduction exceeds 65% (Fehlings and Skaf, 1998). White matter cellular damage has been theorized to be a function of axon cross-sectional area (Kraus, 1996), tissue strain and strain rate (Shi and Whitebone, 2006), or tissue stress state (Henderson et al., 2005).

The objectives of this study were first, to characterize the mechanical response of spinal cord white matter with hyperelastic material parameters and second, to quantitatively establish a link between tissue-level stresses and strains invoked during slow compression and white matter cellular injury.

Section snippets

Tissue acquisition

The dissection procedure used to excise guinea pig spinal cords has been described previously and was approved by the Purdue University Animal Care and Use Committee (Shi and Blight, 1996; Shi and Pryor, 2002; Shi and Whitebone, 2006). Adult guinea pigs were used in this study (body weight: 255–350 g). Following animal sacrifice, spinal cords were removed and dissected to isolate strips of white matter.

Transverse compression of white matter strips

Tissue specimens (n=7), at room temperature, were deformed at 0.05 mm/s to 90% nominal

Results

White matter strip cross-sectional area decreased linearly with increased nominal transverse compression (Fig. 1). The force–deformation responses of the white matter strips (Fig. 2) included an initial toe region where there was no measurable resistance to the applied deformation. Following the toe region, the tissue resistance to additional deformation rapidly increased. The average force magnitude required to achieve 90% nominal transverse compression was 0.246 N (standard deviation: 0.145 N).

Discussion

This study is the first to report material parameters of the spinal cord parenchyma in transverse compression. The nonlinear force–deformation response obtained experimentally for the inhomogeneous guinea pig spinal cord white matter strips necessitated the use of a hyperelastic constitutive relation to model the tissue's elastic response. Bilston and Thibault (1996) fit the stress–strain response obtained for uniaxial tensile tests of human cervical spinal cords to a hyperelastic model

Conflict of interest

The authors have no conflicts of interest to disclose for this manuscript.

Acknowledgments

The authors wish to acknowledge support from the Purdue Research Foundation, Discovery Park at Purdue University, and the State of Indiana, as well as the technical contributions of Gary Leung.

References (21)

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