Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in rats

It has been shown that there is extensive inflammation in the leptomeninges in patients with secondary progressive MS. This is associated with increased sub-pial demyelination, neuronal loss and progression of the disease course. It is not known why this occurs so this study looked at the possibility that pro-inflammatory cytokine production within the meninges may be key to this process.

A model of sub-pial cortical grey matter demyelination was set up in rats. Post-mortem CSF and dissected cerebral leptomeningeal tissue from MS patients was used to look at tumour necrosis factor (TNF), interferon gamma protein and messenger RNA levels.

There was increased expression of the pro-inflammatory cytokines TNF and interferon gamma in the meninges of patients with SPMS. There was extensive sub-pial demyelination and infiltration of lymphocytes into the meninges after the rats were injected with TNF and interferon gamma and they were pre-immunised with a subclinical dose of myelin oligodendrocyte glycoprotein. There was significant microglial/macrophage activation present in a gradient from the pial surface to the deeper cortical layers. Interestingly, demyelination was not seen in the animals immunized with incomplete Freund’s adjuvant and injected with cytokines.

This study demonstrates the role of pro-inflammatory molecules in the meninges involved in cortical demyelination in MS.

Authors: Gardner C, Magliozzi R

Source: Brain. 2013 Oct 30. [Epub ahead of print]

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