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In vivo, tissue-level, mechanical thresholds for axonal injury in the guinea pig optic nerve were determined by comparing morphological injury to estimated in vivo tissue strain. The right optic nerve of adult male guinea pigs was stretched to one of seven ocular displacement levels. Morphological injury was detected three days post-stretch with neurofilament immunohistochemical staining (NF68). A companion set of in situ experiments was used to determine the empirical relationship between ocular displacement and optic nerve stretch. Logistics regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were then used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain- based thresholds for morphological damage to the guinea pig white matter.

Validating a traumatic brain injury finite element model is often limited by a lack of extensive animal injury data that may be used to examine the conditions under which the model is accurate. Given that most published reports specify only general descriptions of injury, this study examined potential evaluation strategies and assessed the ability of a finite element model to simulate the general descriptions of injury in an animal model. The results of this study showed that 1) the results from a simplified finite element model could estimate trends that were similar to the injury patterns observed in a set of animal experiments, 2) a parameter (Z parameter), which quantified the comparison process between computational and animal data, estimated trends that would help in the model evaluation process, and 3) a more complete evaluation process would occur if multiple testing methods were included in the evaluation procedure.

Traumatic brain injury finite element analyses have evolved from crude geometric representations of the skull and brain system into sophisticated models which take into account distinct anatomical features. However, two distinct finite element modeling approaches have evolved to account for the relative motion that occurs between the skull and cerebral cortex during traumatic brain injury. The first and most common approach assumes that the relative motion can be estimated by representing the cerebrospinal fluid inside the subarachnoid space as a low shear modulus, virtually incompressible solid. The second approach assumes that the relative motion can be approximated by defining a frictional interface between the cerebral cortex and dura mater. This study presents data from an experimental model of traumatic brain injury coupled with finite element analyses to evaluate the modeling approach's ability to predict specific forms of traumatic brain injury.

A finite element model of cerebral contusion in the rat was developed and compared to experimental injury maps demonstrating blood-brain barrier (BBB) breakdown. The model was exercised at the nine unique loading conditions used experimentally. Logistic regressions of four variables, maximum principal logarithmic strain (LEP), maximum principal stress (SP), strain energy density (SEN), and von Mises stress (MIS) demonstrated highly significant confidence in the prediction of the 50th percentile values (chi-squared, p<0.00001). However, only values for LEP were invariant across loading conditions. These results suggest that the BBB is most sensitive to LEP, and that breakdown occurs above a strain of 0.188 +/- 0.0324.

Experimental tests using porcine brainstem samples were performed on a custom designed stress relaxation shear device. Tests were performed dynamically at strain rates >1 s−1, to three levels of peak strain (2.5%-7.5%). The directional dependence of the material properties was investigated by shearing both parallel and transverse to the predominant direction of the axonal fibers. Quasi-linear viscoelastic theory was used to describe the reduced relaxation response and the instantaneous elastic function. The time constants of the reduced relaxation function demonstrate no directional dependence; however, the relative magnitude of the exponential functions and the parameter representing the final limiting value are significantly different for each direction. The elastic function qualitatively demonstrates a dependence on direction. These results suggest that the brainstem is an anisotropic material.