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Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Imaging of repeated episodes of demyelination and remyelination in multiple sclerosis
Robert A Brown1, Sridar Narayanan1, Douglas L Arnold1
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, 3801 Rue University, Montreal H3A 2B4, Canada.
Abstract:
Multiple sclerosis (MS) is characterized by the formation of demyelinating lesions in the white matter (WM). However, the timecourse of the evolution of healthy white matter into fully demyelinated lesions in MS is not well understood. We use a recently proposed technique to examine magnetization transfer ratio (MTR) timecourses in lesions segmented from MTR images in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS). In both groups we found MTR lesions forming both in previously normal appearing WM (de novo lesions) as well as in previously lesional tissue that appears to be experiencing a second round of inflammatory demyelination (repeat lesions). Both de novo and repeat lesions exhibited significant, but incomplete MTR recovery, suggesting partial remyelination; post-lesion MTR values in de novo lesions were similar to pre-lesion values in repeat lesions. Both de novo and repeat lesions were found in subjects in relapsing-remitting and secondary progressive stages of MS, and repeat lesions appeared relatively more common in the secondary progressive phase. These observations support the hypothesis that entirely demyelinated lesions found on histopathology are the result of multiple episodes of demyelination and incomplete remyelination, and may have implications for MS treatment development efforts aimed at neuroprotection and enhancing remyelination.
Insights
Multiple sclerosis (MS) lesions evolve over time, with new lesions forming in normal-appearing white matter (WM) and repeat lesions occurring in previously affected areas. Both types show incomplete recovery, suggesting partial remyelination in MS.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Multiple sclerosis (MS) involves demyelination in the brain's white matter (WM).
- The precise timeline of white matter lesion development in MS remains unclear.
- Understanding lesion evolution is crucial for developing effective MS therapies.
Purpose of the Study:
- To investigate the temporal dynamics of white matter lesion formation and evolution in MS.
- To characterize the process of demyelination and remyelination using magnetization transfer ratio (MTR) imaging.
- To differentiate between new (de novo) and recurrent (repeat) lesions in MS patients.
Main Methods:
- Utilized a novel technique to analyze MTR timecourses in segmented white matter lesions.
- Examined MTR data from patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).
- Identified and tracked both de novo and repeat lesions over time.
Main Results:
- Observed MTR lesions forming in previously normal-appearing white matter (de novo lesions).
- Detected repeat lesions in areas previously affected by demyelination, indicating recurrent inflammatory activity.
- Both de novo and repeat lesions demonstrated significant, albeit incomplete, MTR recovery, suggesting partial remyelination.
- Post-lesion MTR values in de novo lesions were comparable to pre-lesion values in repeat lesions.
- Repeat lesions were more prevalent in the secondary progressive MS phase.
Conclusions:
- MS lesions result from multiple episodes of demyelination and incomplete remyelination.
- The findings support a model of lesion development involving repeated inflammatory attacks and partial repair.
- These insights have potential implications for neuroprotective and remyelination-enhancing therapeutic strategies in MS.
