In this study, an in vivo, tissue-level, mechanical threshold for functional injury to central nervous system (CNS) white matter was determined by comparing electrophysiological impairment to estimated tissue strain in an in vivo model of axonal injury. Axonal injury was produced by transiently stretching the right optic nerve of an adult male guinea pig to one of seven levels of ocular displacement (Nlevel=10; Ntotal=70). Functional injury was determined by the magnitude of the latency shift of the N35 peak of the visual evoked potentials (VEPs) recorded before and after stretch. A companion set of in situ experiments (Nlevel= 5) was used to determine the empirical relationship between ocular displacement and optic nerve stretch. Logistic 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, the authors determined three Lagrangian strain-based thresholds for electrophysiological impairment to the optic nerve tissue. The liberal threshold intended to minimize the false positive rate was a strain of 0.28, and the conservative threshold that minimized the false negative rate was 0.13. The optimal threshold criteria that balanced the specificity and sensitivity measures was 0.18. With this threshold data, it is now possible to predict more accurately the conditions that cause diffuse axonal injury in man. (A)
Samenvatting