Fig. 2.

A 2-week therapeutic treatment with BLZ945 after a 5-week cuprizone intoxication period reduced MRI signal in cortex and striatum but not corpus callosum, suggesting increased remyelination. a Schematic diagram of the experimental setup for the therapeutic treatment. Groups consisted of mice treated for 5 weeks with control food (normal food) or 0.2% cuprizone in food and then switched back to control food (normal food) for the 2-week therapeutic treatment (vehicle or BLZ945 169 mg/kg p.o., qd). MRI measurements were performed at week 0 (baseline), week 5 at max. Pathology of cuprizone intoxication, at week 6 (1 week of therapeutic or vehicle treatment on control food) and at week 7 (2 weeks of therapeutic or vehicle treatment on control food). Mice were killed at week 7 immediately after the last MRI measurement. b Representative MRI images acquired from two mice, one receiving 0.2% cuprizone and then normal food with vehicle (upper row) and the other treated with 0.2% cuprizone for 5 weeks with subsequent switch to normal food and BLZ945 treatment (lower row). c Representative MRI images indicating analyzed brain regions (in red). d MRI signal in cortex and striatum for the different treatment groups. For each brain region, MRI signal was normalized to absolute values in the control group (control food, vehicle treatment). e MRI signal and MTR in corpus callosum and external capsule for the different treatment groups (normalized to values in the control group). Because of the small magnitude (≤2%) of MTR reductions in the cortex and striatum following the 5-week cuprizone intoxication period, MTR changes in these areas were not considered here. Grey and black symbols indicate individual values from two independent experiments. Group sizes: control+vehicle (n = 7 from experiment 1, n = 7 from experiment 2), cuprizone+vehicle (n = 6 from experiment 1, n = 6 from experiment 2; one mouse was removed from experiment 2 due to technical reasons), cuprizone+BLZ945 (n = 7 from experiment 1, n = 6 from experiment 2). Data is shown as mean ± SEM. Statistics (for combined experiments): Turkey’s multiple comparison test (***: p < 0.001, ****: p < 0.0001), n.s.: not significant, ctrl: control, cpz: cuprizone, cc: corpus callosum, ec: external capsule, MRI: magenetic resonance imaging, MTR: magnetization transfer ratio