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Open AccessArticle

Comparison of Theiler’s Murine Encephalomyelitis Virus Induced Spinal Cord and Peripheral Nerve Lesions Following Intracerebral and Intraspinal Infection

1
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
2
Center for Systems Neuroscience, 30559 Hannover, Germany
3
Department of Neurogenetics, Max-Planck-Institute for experimental Medicine, 37075 Göttingen, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally first to this article.
Int. J. Mol. Sci. 2019, 20(20), 5134; https://doi.org/10.3390/ijms20205134
Received: 24 September 2019 / Revised: 14 October 2019 / Accepted: 15 October 2019 / Published: 16 October 2019
Hallmarks of Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) include spinal cord (SC) inflammation, demyelination and axonal damage occurring approximately 5–8 weeks after classical intracerebral (i.c.) infection. The aim of this study was to elucidate the consequences of intraspinal (i.s.) TMEV infection and a direct comparison of classical i.c. and intraspinal infection. Swiss Jim Lambert (SJL)-mice were i.s. infected with the BeAn strain of TMEV. Clinical investigations including a scoring system and rotarod analysis were performed on a regular basis. Necropsies were performed at 3, 7, 14, 28 and 63 days post infection (dpi) following i.s. and at 4, 7, 14, 28, 56, 98, 147 and 196 dpi following i.c. infection. Serial sections of formalin-fixed, paraffin-embedded SC and peripheral nerves (PN) were investigated using hematoxylin and eosin (HE) and immunohistochemistry. I.s. infected mice developed clinical signs and a deterioration of motor coordination approximately 12 weeks earlier than i.c. infected animals. SC inflammation, demyelination and axonal damage occurred approximately 6 weeks earlier in i.s. infected animals. Interestingly, i.s. infected mice developed PN lesions, characterized by vacuolation, inflammation, demyelination and axonal damage, which was not seen following i.c. infection. The i.s. infection model offers the advantage of a significantly earlier onset of clinical signs, inflammatory and demyelinating SC lesions and additionally enables the investigation of virus-mediated PN lesions. View Full-Text
Keywords: Theiler’s murine encephalomyelitis virus-induced demyelinating disease; inflammation; intraspinal infection; peripheral nerve lesions Theiler’s murine encephalomyelitis virus-induced demyelinating disease; inflammation; intraspinal infection; peripheral nerve lesions
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Jin, W.; Leitzen, E.; Goebbels, S.; Nave, K.-A.; Baumgärtner, W.; Hansmann, F. Comparison of Theiler’s Murine Encephalomyelitis Virus Induced Spinal Cord and Peripheral Nerve Lesions Following Intracerebral and Intraspinal Infection. Int. J. Mol. Sci. 2019, 20, 5134.

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