Wednesday, 18 March 2015

MTR for may not be so good for demyelination.

Fjær S, Bø L, Myhr KM, Torkildsen Ø, Wergeland S. Magnetization transfer ratio does not correlate to myelin content in the brain in the MOG-EAE mouse model. Neurochem Int. 2015 Mar 2. pii: S0197-0186(15)00034-0

Magnetization transfer ratio (MTR) is a magnetic resonance imaging (MRI) method, which may detect demyelination not detected by conventional MRI in the central nervous system of patients with multiple sclerosis (MS). A decrease in MTR value has previously been shown to correlate to myelin loss in the mouse cuprizone model for demyelination. In this study, we investigated the sensitivity of MTR for demyelination in the myelin oligodendrocyte (MOG) 1-125 induced experimental autoimmune encephalomyelitis (EAE) mouse model. A total of 24 female C57BL/6 mice were randomized to a control group (N = 6) or EAE (N = 18). MTR images were obtained at a preclinical 7 Tesla Bruker MR-scanner before EAE induction (baseline), 17-19 days (midpoint) and 31-32 days (endpoint) after EAE induction. Mean MTR values were calculated in five regions of the brain and compared to weight, EAE severity score and myelin content assessed by immunostaining for proteolipid protein and luxol fast blue, lymphocyte and monocyte infiltration and iron deposition. Contrary to what was expected, MTR values in the EAE mice were higher than in the control mice at the midpoint and endpoint. No significant difference in myelin content was found according to histo- or immunohistochemistry. Changes in MTR values did not correlate to myelin content, iron content, lymphocyte or monocyte infiltration, weight or EAE severity scores. This suggest that MTR measures of brain tissue can give significant differences between control mice and EAE mice not caused by demyelination, inflammation or iron deposition, and may not be useful surrogate markers for demyelination in the MOG1-125 mouse model.

MTR is an outcome that a number of remyelination trials n MS are banking on. In this study in EAE it suggests that MTR imGING My not be that good for looking a demyelination. If this is true then the trials may struggle to find a difference. However, the demyelination in C57BL/6 mice is unlike demyelination in MS and and may be masked by a lot of axonal loss. Time will tell

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