| Abstract No.: | A-C1081 |
| Country: | Canada |
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| Title: | A COMPARISON OF CHRONIC AND RELAPSING-REMITTING FORMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. |
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| Authors/Affiliations: | 1 Jennifer Berard*; 1 Samuel David
1 Center for Research in Neuroscience, McGill University Health Center, Montreal, QC, Canada
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| Content: | Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Like MS, the animal model experimental autoimmune encephalomyelitis (EAE) is also characterized by CNS inflammation and demyelination and can follow either a relapsing-remitting (RR) or a chronic-progressive (CH) disease course. Thus far, comparisons between RR- and CH-EAE have not been done in the same animal strain using the same antigen, making the findings difficult to interpret.
Objectives:
To better understand the differences between RR- and CH-EAE by comparing these models in the same strain of mouse using the same myelin antigen.
Materials and Methods:
EAE was induced in female C57BL/6 mice (8-10 weeks) by subcutaneous injections of MOG35-55 in CFA supplemented with M. tuberculosis, followed by IV injections of Pertussis toxin on Days 0 and 2. RR- and CH-EAE were induced by varying the concentrations of MOG, M. tuberculosis, and Pertussis toxin. Animals were sacrificed at the onset (grade 1) and peak (grade 4) stages of EAE, as well as at the time-point corresponding to remission in the RR group (Days 21-26). Various disease parameters were assessed at each of these time points.
Results:
In the RR model, the lesion burden increases 2-fold between the onset and peak, followed by a 4-fold reduction at remission. In contrast, in the CH model, the lesion burden increases 4.5-fold between the onset and peak, followed by an additional 1.6-fold increase at the time-point corresponding to remission in the RR model. Myelin loss assayed by Luxol fast blue (LFB) staining showed that in RR-EAE, signs of myelin loss were detected at the peak of disease, followed by a reduction in remission, suggesting recovery by remyelination. In CH-EAE, the extent of myelin loss at peak was 0.5-fold higher than in RR-EAE. In CH-EAE, at the time-point corresponding to remission in RR-EAE, there was an additional 3-fold increase in myelin loss, indicating on-going myelin destruction. FACS analysis showed that the number of CD4+ T cells, macrophages, and microglia were similar at the peak in both RR- and CH-EAE. However, the number of CD8+ T cells was nearly 2-fold greater in CH- than in RR-EAE. In addition, protein expression of IL-1α was significantly increased in CH-EAE, as compared to RR-EAE.
Conclusion:
These data reveal interesting cellular and molecular differences between CH- and RR-EAE.
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