Ac. Bain et Df. Meaney, Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury, J BIOMECH E, 122(6), 2000, pp. 615-622
Citations number
71
Categorie Soggetti
Multidisciplinary
Journal title
JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME
In vivo, tissue-level, mechanical thresholds for axonal injury were determi
ned by comparing morphological injury and electrophysiological impairment t
o estimated tissue strain in an in vivo model of axonal injury. Axonal inju
ry was produced by-dynamically stretching the right optic nerve of an adult
male guinea pig to one of seven levels of ocular displacement (N-level=10;
N-total=70). Morphological injury was detected with neurofilament immunohi
stochemical staining (NF68, SM132). Simultaneously, functional injury was d
etermined by the magnitude of the latency shift of the N-35 peak of the the
visual evoked potentials (VEPs) recorded before and after stretch. A compa
nion set of in situ experiments (N-level=5) was used to determine the empir
ical relationship between the applied ocular displacement and the magnitude
of optic nerve stretch. Logistic regression analysis, combined with sensit
ivity and specificity measures and receiver operating characteristic (ROC)
curves were used to predict strain thresholds for axonal injury. From this
analysis, we determined three Lagrangian strain-based thresholds for morpho
logical damage to white matter The liberal threshold, intended to minimize
the detection of false positives, was a strain of 0.34, and the conservativ
e threshold strain that minimized the false negative rate was 0.14. The opt
imal threshold strain criterion that balanced the specificity and sensitivi
ty measures was 0.21. Similar comparisons for electrophysiological impairme
nt produced liberal, conservative; and optimal strain thresholds of 0.28 0.
13, and 0.18, respectively. With these threshold data, it is now possible t
o predict more accurately the conditions that cause axonal injury in human
white matter.