Escalating disease in GFAPcR1D mice coincided with focal areas of intense inflammation in spinal cords, which contrasted with the more diffuse inflammation in wt mice (Fig. 6 ). Demyelination was also increased with myelin loss encompassing 5.761.8% of spinal cord area in GFAPcR1D mice versus 2.361.4% in wt mice (p#0.05) at day 35 p.i. (Fig. 6 ). The demyelinated areas further exhibited enhanced axonal damage in GFAPcR1D mice (Fig. 6) , supporting a correlation between enhanced tissue damage, sustained morbidity and increased mortality ( Fig. 1A ; Table 1 ). Astrocyte activation associated with areas of myelin loss is a prominent finding in the CNS of both patients with MS and rodents with EAE. Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). By contrast, the frequency of activated astrocytes in spinal cord grey matter areas that were not associated with demyelinated lesions, was increased in GFAPcR1D mice with 101.5623.0 GFAP + activated astrocytes/mm 2 versus 25.5615.5 in wt mice (p,0.001) (Fig. 7) . A similar increase in astrocyte activation within grey matter distal to white matter lesions was also detected in GFAPcR1D SJL mice during chronic EAE (data not shown).