Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesBreast cancer stem cell (BCSC) line #1 and #4 were grown in either stem cell medium or medium favoring the differentiation. Cells were genetically labeled with fluorescent protein expression cassettes and xenotransplanted into immunocompromised mice, giving rise to tumors. Tumors were explanted, dissociated and kept in culture so as to isolate growing cells. Cells were then sorted for fluorescent protein expression and RNA was extracted.
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