DIGITIZED IMAGE-ANALYSIS REVEALS DIFFUSE ABNORMALITIES IN NORMAL-APPEARING WHITE-MATTER DURING ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Demyelination of the central nervous system is a hallmark of multiple sclerosis and its widely used animal model, experimental autoimmune en cephalomyelitis (EAE), Recent studies using magnetic resonance imaging and spectroscopy on multiple sclerosis patients have revealed abnorma lities of central nervous system normal-appearing white matter suggest ing that micro-demyelination and/or extensive membrane turnover accomp anies and perhaps precedes the appearance of manifest inflammatory les ions, In the present study, we induced EAE in SWXJ mice and analyzed d igitized images of immunocytochemically stained spinal cord for detect ion of myelin proteolipid protein (PLP), We found that digitized image analysis is a highly sensitive, objective methodology for measuring t he extent of myelin loss during EAE, Our data show that two-thirds of the measured reduction of myelin PLP occurring in EAE spinal cord coul d be attributed to a loss of myelin in normal-appearing white matter. The marked decrease in detection of PLP was accompanied by a correspon ding decrease in PLP mRNA in the central nervous system. Our results i ndicate that during acute EAE, diffuse myelin abnormalities extend far beyond visibly detectable inflammatory foci and are characterized by a global decrease in the expression of myelin genes and their encoded proteins. (C) 1998 Wiley-Liss, Inc.