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Updated: Jul 11, 2026
Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord
Published on: February 22, 2015
Targeting inflammatory demyelinating lesions to sites of Wallerian degeneration
Ikuo Tsunoda1, Tomoko Tanaka, Yukio Saijoh
1Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84132-2305, USA.
Abstract:
In Theiler's murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).
Insights
Axonal injury in Theiler
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection serves as a model for multiple sclerosis (MS).
- In TMEV infection, axonal damage precedes inflammatory demyelination, suggesting a link between the two processes.
Purpose of the Study:
- To investigate the hypothesis that axonal damage recruits inflammatory cells, leading to demyelination.
- To explore the 'Inside-Out' model of lesion development in TMEV-induced demyelination.
Main Methods:
- Induction of axonal degeneration in TMEV-infected mice using Ricinus communis agglutinin (RCA) I injection into the sciatic nerve.
- Examination of neuropathology 1 week after RCA I injection.
- Comparison of lesion development in TMEV-infected mice with and without RCA I, and in control mice receiving RCA I alone.
Main Results:
- RCA I injection induced inflammatory lesions in the posterior funiculus of TMEV-infected mice, in addition to lesions in the anterior/lateral funiculi.
- Control mice (TMEV-infected without RCA I, or RCA I alone) did not develop inflammatory lesions in the posterior funiculus.
- No significant differences in lymphoproliferative responses or TMEV antibody titers were observed among groups.
Conclusions:
- Axonal degeneration contributes to inflammatory cell recruitment into the central nervous system by altering the local microenvironment.
- This supports an 'Inside-Out' model where lesions develop from the axon outwards to the myelin.
- Axonal injury plays a critical role in initiating demyelinating lesions in this multiple sclerosis model.
