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Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination
Ikuo Tsunoda1, Robert S Fujinami
1Department of Neurology, 3R330 School of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, Utah 84132-2305, USA.
Springer Seminars in Immunopathology
|December 28, 2002
Summary
Multiple sclerosis (MS) may involve direct axonal injury, not just secondary damage. Axonal injury might trigger demyelination, suggesting an "Inside-Out" disease model in MS.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) traditionally targets myelin or oligodendrocytes.
- Axonal injury in MS is typically considered secondary to myelin damage (Outside-In model).
- Recent findings show gray matter lesions and axonal injury in normal-appearing white matter in MS.
Purpose of the Study:
- To investigate if axonal injury in MS is exclusively secondary or can be a primary event (axonopathy).
- To explore if axonal injury can initiate secondary damage, including demyelination.
- To challenge the traditional Outside-In model of MS pathology.
Main Methods:
- Review of existing literature on MS and viral infections causing demyelination.
- Comparison of pathological mechanisms in MS and spinal cord injury (SCI).
- Analysis of neurofilament immunostaining in an animal model of MS (Theiler's murine encephalomyelitis virus infection).
Main Results:
- Axonal damage is observed in viral infections that also cause demyelination.
- Spinal cord injury shows axonal injury preceding oligodendrocyte apoptosis and demyelination.
- In an MS animal model, axonal injury and oligodendrocyte apoptosis precede demyelination.
Conclusions:
- Axonal injury may be a primary event in MS, not solely secondary.
- Axonal injury could trigger demyelination, supporting an Inside-Out model.
- This challenges the conventional understanding of MS pathogenesis.