Author Of 1 Presentation
PS14.05 - Remyelinating satellite oligodendrocytes provide a rescue strategy to protect neurons after cortical demyelination in multiple sclerosis
Abstract
Background
Remyelination is observed in the white and grey matter of patients with multiple sclerosis (MS). However, whether remyelinating oligodendrocytes arise from newly formed oligodendrocyte progenitor cells (OPCs) or from preexisting OPCs generated during development is not known.
Objectives
The aim of the study is to investigate the origin of remyelinating oligodendrocytes in MS. Therefore, we intensively studied oligodendrocytes, oligodendrocyte-proliferation and differentiation in MS and demyelinating models of MS.
Methods
We performed immunohistochemistry in white and grey matter lesions of patients with early MS obtained at biopsy and late cortical lesions of patients with progressive MS obtained at autopsy. In comparison, we analyzed experimental models of MS, targeting the cortex or the white matter.
Results
In experimental demyelination as well as MS we found very little proliferation of oligodendrocytes and only single mature oligodendrocytes with BrdU incorporation indicating that newly formed oligodendrocytes did not participate in remyelination. Actively remyelinating, breast carcinoma amplified sequence 1 (BCAS1)-positive oligodendrocytes were to identify active remyelination and find that BCAS1 positive myelinating oligodendrocytes were generated immediately after experimental lesion induction and in early active MS lesions. In MS, the total number of oligodendrocytes in the cerebral cortex of early active MS lesions remained unchanged, but decreased with disease duration. This was associated with increased numbers of TPPP/p25 mature oligodendrocytes, suggesting oligodendrocyte differentiation. Furthermore, we identified that a fraction of BCAS1 positive oligodendrocytes in the cerebral cortex are perineuronal satellite cells. These cells obtain a myelinating morphology and express MAG after toxic demyelination and in early MS indicating that these cells participate in remyelination. In progressive MS and at late remyelination time-points in animal models we observed increased numbers of TPPP/p25 positive satellite oligodendrocytes.
Conclusions
Our data show that remyelination is predominantly performed by preexisting oligodendrocytes and is most efficient immediately after demyelination. Furthermore, we were able to demonstrate for the first time that BCAS1 positive perineuronal satellite cells in the cerebral cortex serve as a pool to generate remyelinating oligodendrocytes after experimental demyelination and in MS.
Author Of 1 Presentation
P0610 - Multiparametric MRI investigation of enlarging and shrinking MS lesions (ID 1876)
Abstract
Background
Background: After cessation of contrast enhancement MS lesions may show enlargement or shrinkage on T1w MRI. The presence of hypointense lesion rims on susceptibility weighted MRI may be associated with ongoing inflammation and tissue damage/rearrangement. The relationship of enlarging and shrinking MS lesions on T1w MRI to hypointense rims on SWI is therefore of interest.
Objectives
Objective: To investigate enlarging and shrinking non-enhancing multiple sclerosis (MS) lesion characteristics using a novel multimodal magnetic resonance imaging (MRI) approach.
Methods
Methods: Two high-resolution 3 D T1-weighted 3T MRI datasets obtained 12 months apart were analyzed in 67 MS patients. Non-enhancing enlarging and shrinking lesions were identified by voxel guided morphometry (VGM) demonstrating regional volume changes as compared to stable lesions without volume change. In addition the presence of hypointense lesion rims on susceptibility-weighted imaging (SWI) was evaluated. In order to estimate tissue damage within lesions, T1 signal intensity (SI) ratios and the apparent diffusion coefficient (ADC) were analyzed.
Results
Results: Forty-three patients demonstrated chronic enlarging and/or shrinking lesions (active T1 lesions), while in 24 patients exclusively stable lesions were seen. Overall, we identified 444 chronic MS lesions (109 enlarging, 67 shrinking, 268 stable lesions). Chronic-enlarging/shrinking lesions were more frequently associated with hypointense rims compared to stable lesions (p < 0.05). Both, chronic-enlarging/shrinking lesions showed a stronger decrease of the T1 SI ratio and, conversely, an increase in ADC values at follow-up in comparison to stable lesions. Patients with enlarging or shrinking lesions had longer disease durations, higher EDSS scores, larger T2 lesion volumes and lower normalized brain volumes than patients without such lesions (p < 0.05).
Conclusions
Conclusion: Enlarging and shrinking lesions on T1w MRI frequently show hypointense rims on SWI. Those lesions are linked to progressive white matter damage and may indicate sustained inflammation and may therefore indicate low grade inflammatory changes, that could be a valuable marker of disease activity.