Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

@article{Meinl2008CompartmentalizationOI,
  title={Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis},
  author={Edgar Meinl and Markus Krumbholz and Tobias Derfuss and Andreas Junker and Reinhard Hohlfeld},
  journal={Journal of the Neurological Sciences},
  year={2008},
  volume={274},
  pages={42-44}
}
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References

SHOWING 1-10 OF 32 REFERENCES
Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology.
TLDR
Data support an immunopathogenetic mechanism whereby B-cell follicles developing in the multiple sclerosis meninges exacerbate the detrimental effects of humoral immunity with a subsequent major impact on the integrity of the cortical structures.
B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation
TLDR
These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands and outline the possibly double‐edged effects of B cells and immunoglobulin in the CNS.
Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis.
TLDR
This study suggests that a compartmentalized B cell response occurs within the CNS during an ongoing inflammatory reaction, through a recapitulation of all stages of B cell differentiation observed in secondary lymphoid organs.
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain
TLDR
Findings from this study are interpreted as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.
Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis
Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum
Multiple sclerosis: T-cell receptor expression in distinct brain regions.
TLDR
P pervasive T-cell clones exist in distinct regions of MS brain, and these clones are 'private' (unique) to individual patients, supporting the pathogenic relevance of this T- cell subset.
Cortical demyelination and diffuse white matter injury in multiple sclerosis.
TLDR
Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis
TLDR
A serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis treated with methylprednisolone and 26 patients treated with placebo in two randomized controlled trials is reported, suggesting differential involvement of CX CL10 andCCL2 in CNS inflammation.
Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment.
TLDR
The strong linkage of CXCL13 to immune cells and immunoglobulin levels in CSF suggests that this is one of the factors that attract and maintain B and T cells in inflamed CNS lesions.
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