Abstract
Assessment of myelin integrity in peripheral nerve injuries and pathologies has largely been limited to post-mortem analysis owing to the difficulty in obtaining biopsies without affecting nerve function. This is further encumbered by the small size of the tissue and its location. Therefore, the development of robust, non-invasive methods is highly attractive. In this study, we used magnetic resonance imaging (MRI) techniques, including magnetization transfer ratio (MTR), to longitudinally and non-invasively characterize both the sciatic nerve crush and lysolecithin (LCP) demyelination models of peripheral nerve injury in rodents. Electrophysiological, gene expression and histological assessments complemented the extensive MRI analyses in young and aged animals. In the nerve crush model, MTR analysis indicated a slower recovery in regions distal to the site of injury in aged animals, as well as incomplete recovery at six weeks post-crush when analyzing across the entire nerve surface. Similar regional impairments were also found in the LCP demyelination model. This research underlines the power of MTR for the study of peripheral nerve injury in small tissues such as the sciatic nerve of rodents and contributes new knowledge to the effect of aging on recovery after injury. A particular advantage of the approach is the translational potential to human neuropathies.
Highlights
Diagnosis of demyelination or dysmyelination carries important therapeutic and prognostic implications
Injured nerves exhibited marked enlargement and hyperintense signal at week 1 postoperatively. Such images were used for defining the regions-of-interest (ROIs) for magnetization transfer ratio (MTR) analyses
When applying MTR for the study of the sciatic nerve recovery after injury, the nerve was analyzed as a whole or by sub-dividing it in 4 regions, named R1 to R4 (Fig. 1b)
Summary
Diagnosis of demyelination or dysmyelination carries important therapeutic and prognostic implications. Contrast agents, including gadofluorine M and superparamagnetic iron oxide particles, allow the visualization of both the dynamics of peripheral nerve injury and its repair[18,19] and of macrophage infiltration[20], respectively Both have been used to increase specificity in experimental models. MTR of the sciatic nerve was complemented by in vivo electrophysiology and toe spread assessments, as well as by post-mortem histology and gene expression analyses in a murine sciatic nerve crush (SNC) model. These were correlated with the corresponding changes in muscle. A second model of demyelination by local injection of lysolecithin (LCP) in rat sciatic nerve was included for comparison
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