Inflammation in spinal cords from the GFAPcR1D mice was also similar to wt controls at the peak of clinical symptoms (Fig. 4) . Although numbers and distribution of CD4 + T cells were also similar (4.661.3/mm 2 in GFAPcR1D mice vs. 3.860.1/ mm 2 in wt mice; Fig. S1 ), spinal cords of GFAPcR1D mice exhibited a ,2-fold increase in demyelination (Fig. 4) . Areas of demyelination encompassed 7.361.0% of spinal cord white matter in GFAPcR1D mice versus 3.860.9% in wt mice (p#0.01). Furthermore, the increase in demyelination was associated with a prominent loss of axons in GFAPcR1D mice compared to controls (Fig. 4) . Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although CCL5, IL-1 and TNF mRNA expression were increased in the spinal cords of the GFAPcR1D mice, no differences in IFN-c, iNOS, CXCL10 or IL-6 mRNA were consistent with similar inflammation (Fig. 5) . These data suggest that the initial disease pathogenesis, reflected by an increased demyelination in spinal cords, but not brain, during ascending paralysis is dampened by IFN-c signaling to astrocytes.