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Comparison of Reported Spinal Cord Lesions in Progressive Multiple Sclerosis with Theiler's Murine Encephalomyelitis

Eva Leitzen1,2, Wen Jin3,4, Vanessa Herder5,6

  • 1Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany. Eva.Leitzen@tiho-hannover.de.

International Journal of Molecular Sciences
|March 3, 2019
PubMed
Abstract

Insights

Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) in mice shows spinal cord lesions similar to multiple sclerosis (MS). This study confirms TMEV-IDD is a suitable model for investigating progressive MS spinal cord pathology.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Spinal cord (SC) lesions in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) share key features with progressive multiple sclerosis (MS) brain lesions, including inflammation, demyelination, and axonal damage.
  • Understanding these similarities is crucial for developing effective MS treatments.

Purpose of the Study:

  • To compare spinal cord lesions in MS and TMEV-IDD.
  • To analyze the spatial and temporal distribution of demyelination, inflammation, SC atrophy (SCA), and axonal degeneration in major descending motor pathways.

Main Methods:

  • Mice were infected with TMEV or mock-infected and monitored weekly.
  • SC tissues were collected at multiple time points post-infection (42, 98, 147, 196 days).
  • Histological analyses included HE staining, immunohistochemistry (myelin basic protein, Mac3, phosphorylated neurofilaments), and transmission electron microscopy.

Main Results:

  • Demyelination was prominent in SC white matter in TMEV-IDD, unlike MS's predominant gray matter involvement.
  • TMEV-infected mice exhibited significant axonal loss, mirroring MS.
  • Ultrastructural findings in TMEV-IDD included denuded axons, myelin degeneration, axonal degeneration, and remyelination.
  • Spinal cord atrophy (SCA), common in MS, was also observed in TMEV-IDD at later time points.

Conclusions:

  • The TMEV-IDD model effectively replicates progressive spinal cord lesions seen in MS.
  • This study supports the utility of TMEV-IDD for investigating MS pathology and potential therapeutic strategies.
Keywords:
Theiler’s murine encephalomyelitis virusaxonal lossmultiple sclerosisreticulospinal tractspinal cordspinal cord atrophy

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