Abstract
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.
Highlights
Theiler’s murine encephalomyelitis virus (TMEV), a member of the Picornaviridae family, induces a demyelinating leukomyelitis after intracerebral (i.c.) infection of susceptible mouse strains like Swiss Jim Lambert (SJL) [1,2,3]
TMEV infection, mice showed significant clinical signs starting at 11 days post infection
TMEV-infected animals showed a deterioration of motor coordination starting at 14 dpi (Figure 1B)
Summary
Theiler’s murine encephalomyelitis virus (TMEV), a member of the Picornaviridae family, induces a demyelinating leukomyelitis after intracerebral (i.c.) infection of susceptible mouse strains like Swiss Jim Lambert (SJL) [1,2,3]. TMEV-IDD represents a well-established animal model for demyelinating diseases in humans, especially resembling important features of the progressive forms of multiple sclerosis (MS) [6,7,8]. This immune-mediated, inflammatory disease of the central nervous system (CNS) constitutes the most frequent cause of non-traumatic neurological disease of young people, and shows an increasing incidence worldwide [9,10,11]. Resistant B6 mice showed a fast onset of persistent clinical signs as well as inflammatory and demyelinating SC lesions, comparable to those seen in TMEV-IDD, and within a markedly shortened time period of about two weeks [22]
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