Stiftung Tierärztliche Hochschule Hannover (TiHo)

Comparison of reported spinal cord lesions in progressive multiple sclerosis with Theiler's murine encephalomyelitis virus induced demyelinating disease

Leitzen, Eva; Jin, Wen ORCID; Herder, Vanessa GND; Beineke, Andreas GND; Elmarabet, Suliman Ahmed; Baumgärtner, Wolfgang GND; Hansmann, Florian GND

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 axonal damage. 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 axonal degeneration/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 (axonal damage) 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 axons similar to MS. Ultrastructural analysis in TMEV-IDD revealed denuded axons, degenerative myelin changes, axonal degeneration, 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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Leitzen, Eva / Jin, Wen / Herder, Vanessa / et al: Comparison of reported spinal cord lesions in progressive multiple sclerosis with Theiler's murine encephalomyelitis virus induced demyelinating disease. 2019.

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