Ja. Kawczak et al., DIGITIZED IMAGE-ANALYSIS REVEALS DIFFUSE ABNORMALITIES IN NORMAL-APPEARING WHITE-MATTER DURING ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Journal of neuroscience research, 54(3), 1998, pp. 364-372
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.