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Digitized image analysis reveals diffuse abnormalities in normal-appearing white matter during acute experimental
J A Kawczak1, P M Mathisen, J A Drazba
1Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
Journal of Neuroscience Research
|November 18, 1998
Summary
In experimental autoimmune encephalomyelitis (EAE), myelin loss occurs in normal-appearing white matter, not just visible lesions. This suggests widespread central nervous system demyelination precedes and accompanies multiple sclerosis progression.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is characterized by central nervous system (CNS) demyelination.
- Experimental autoimmune encephalomyelitis (EAE) is a common animal model for MS.
- Recent studies suggest micro-demyelination in normal-appearing white matter (NAWM) in MS patients.
Purpose of the Study:
- To investigate myelin loss in NAWM during EAE.
- To quantify myelin proteolipid protein (PLP) reduction in EAE spinal cords.
- To correlate myelin loss with gene expression changes.
Main Methods:
- Induction of EAE in SWXJ mice.
- Immunocytochemical staining for PLP in spinal cord tissue.
- Digitized image analysis for myelin quantification.
- Measurement of PLP mRNA levels.
Main Results:
- Digitized image analysis proved a sensitive method for measuring myelin loss in EAE.
- Two-thirds of PLP reduction was observed in NAWM.
- Decreased PLP levels correlated with reduced PLP mRNA expression in the CNS.
Conclusions:
- Diffuse myelin abnormalities in EAE extend beyond inflammatory lesions.
- Widespread demyelination and decreased myelin gene expression characterize acute EAE.
- These findings highlight the importance of NAWM changes in MS pathogenesis.