Comparison of Reported Spinal Cord Lesions in Progressive Multiple Sclerosis with Theiler’s Murine Encephalomyelitis Virus Induced Demyelinating Disease
2019
Background: Spinal cord (SC) lesions in Theiler’s murine encephalomyelitis virus induced
demyelinating disease(TMEV-IDD) resemble important features of brain lesions in progressive multiple sclerosis (MS) including inflammation, demyelination, and
axonaldamage. The aim of the present study was a comparison of SC lesions in MS and TMEV-IDD focusing on spatial and temporal distribution of demyelination, inflammation, SC atrophy (SCA), and
axonaldegeneration/loss in major descending motor pathways. Methods: TMEV and mock-infected mice were investigated clinically once a week. SC tissue was collected at 42, 98, 147, and 196 days post infection, and investigated using hematoxylin and eosin (HE) staining, immunohistochemistry targeting
myelin basic protein(demyelination), Mac3 (microglia/macrophages), phosphorylated
neurofilaments(
axonaldamage) and transmission electron microscopy. Results: Demyelination prevailed in SC white matter in TMEV-IDD, contrasting a predominant gray matter involvement in MS. TMEV-infected mice revealed a significant loss of
axonssimilar to MS. Ultrastructural analysis in TMEV-IDD revealed denuded
axons, degenerative myelin changes,
axonaldegeneration, as well as
remyelination. SCA is a consistent finding in the SC of MS patients and was also detected at a late time point in TMEV-IDD. Conclusion: This comparative study further indicates the suitability of TMEV-IDD as animal model also for the investigation of progressive SC lesions in MS.
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