Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration

This study from Italy investigated the synaptic mechanism of inflammatory neurodegeneration in progressive forms of MS. The study included 20 people with progressive MS, 81 with RRMS and 33 controls and CSF was analysed for cytokines and neurofilament light. The researchers then performed in vitro electrophysiology and cell swelling experiments to measure the effects of inflammatory cytokines in the CSF on synaptic transmission and neuronal integrity.

They found that only tumour necrosis factor (TNF) was significantly higher in progressive MS compared with people with RRMS and control subjects. TNF concentrations were very similar in people with RRMS and in controls. Also, there was no significant difference among people with RRMS during the relapsing or remitting phases of the disease. This demonstrates that TNF is a rather specific CSF marker of progressive MS but not RRMS.

In mouse brain slices incubated in the presence of CSF from progressive MS, the researchers found increased spontaneous excitatory postsynaptic currents (sEPSCs) and glutamate-mediated neuronal swelling through a mechanism dependent on enhanced TNF signalling. Interestingly, following intrathecal rituximab (causing a depletion of B cells), there was a dramatic reduction of TNF levels, of TNF-induced sEPSC alterations, and of neurofilament CSF concentrations in people with progressive MS.

Authors: Rossi S, Motta C
Source: Mult Scler. 2013 Jul 25. [Epub ahead of print]

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