Injection of the sciatic nerve with TMEV: A new model for peripheral nerve demyelination

Abstract

Demyelination of the human peripheral nervous system (PNS) can be caused by diverse mechanisms including viral infection. Despite association of several viruses with the development of peripheral demyelination, animal models of the condition have been limited to disease that is either autoimmune or genetic in origin. We describe here a model of PNS demyelination based on direct injection of sciatic nerves of mice with the cardiovirus, Theiler's murine encephalomyelitis virus (TMEV). Sciatic nerves of FVB mice develop inflammatory cell infiltration following TMEV injection. Schwann cells and macrophages are infected with TMEV. Viral replication is observed initially in the sciatic nerves and subsequently the spinal cord. Sciatic nerves are demyelinated by day 5 post-inoculation (p.i.). Injecting sciatic nerves of scid mice resulted in increased levels of virus recovered from the sciatic nerve and spinal cord relative to FVB mice. Demyelination also occurred in scid mice and by 12 days p.i., hindlimbs were paralyzed. This new model of virus-induced peripheral demyelination may be used to dissect processes involved in protection of the PNS from viral insult and to study the early phases of lesion development.

The L-Coding Region of the DA Strain of Theiler's Murine Encephalomyelitis Virus Causes Dysfunction and Death of Myelin-Synthesizing Cells

“…These abnormalities may have led to the paralysis and subsequent death of mice treated early with tamoxifen. Although peripheral nerve pathology is not a feature of mice infected intracerebrally with DA virus, intrasciatic nerve injection with DA virus is known to cause peripheral nerve demyelination (8). The peripheral nerve disease in tamoxifen-treated DAL/Cre (and DA/Cre) transgenic mice tended to be more prominent than the CNS disease; for example, there were more cells that had prominent activated caspase-3 antibody staining in the nerve roots (Fig.…”

A Subgenomic Segment of Theiler's Murine Encephalomyelitis Virus RNA Causes Demyelination

“…There was evidence of demyelinated peripheral nerves with abnormalities of Schwann cells and oligodendrocytes. A recent report has demonstrated that DA can cause Schwann cell death and peripheral nerve demyelination (3). The finding of abnormalities of myelinsynthesizing cells and demyelination in the DA/Cre mouse in the absence of inflammatory pathology demonstrates that DA viral genes can cause abnormalities of myelin-synthesizing cells and demyelination without a contribution from the immune system.…”

Pathogenesis of Theiler’s murine encephalomyelitis virus‐induced disease

“…There were also abnormalities of the Schwann cells and oligodendrocytes along with peripheral, as well as CNS, demyelination. Of note, DA virus infection is known to cause Schwann cell death and peripheral nerve demyelination (after sciatic nerve injection) in addition to CNS demyelination (after intracerebral inoculation) 44 …”

“…Of note, DA virus infection is known to cause Schwann cell death and peripheral nerve demyelination (after sciatic nerve injection) in addition to CNS demyelination (after intracerebral inoculation). 44 Of interest was the finding that the transgenic mice treated with tamoxifen at a later age expressed the DA recombined transgene for >4 months -so that the toxic gene can be present and cause dysfunction without cell death. Interestingly, this disturbance of luxury function of differentiated cells without cell death, a concept most prominently discussed by Oldstone et al, 45 might be similar to the DA persistent virus infection in which there is chronic demyelination with a restricted virus gene expression (and little viral protein production).…”