Journal of Neuropathology and Experimental
Neurology: Vol. 61, No. 1, pp. 23–32
Jerome R. Wujek, PhD, Carl Bjartmar,
MD, PhD, Edward Richer, BA, Richard M. Ransohoff, MD, Min Yu, MD, Vincent
K. Tuohy, PhD, and Bruce D. Trapp, PhD
Abstract
Multiple sclerosis (MS) is an inflammatory
demyelinating disease of the central nervous system (CNS).
Most patients undergo an initial
relapsing-remitting (RR-MS) course that transforms into a relentless neurodegenerative
disorder, termed secondary progressive (SP)-MS.
Reversible inflammation and demyelination
account readily for the pattern of RR-MS but provide an unsatisfactory
explanation for irrevocable decline in SP-MS.
Axon loss is thought to be responsible
for progressive, non-remitting neurological disability during SP-MS.
There is considerable potential for
neuroprotective therapies in MS, but their application awaits animal models
in which axonal loss correlates with permanent neurological disability.
In this report, we describe quantitative
immunohistochemical methods that correlate inflammation and axonal loss
with neurological disability in chronic-relapsing experimental autoimmune
encephalomyelitis (EAE).
At first attack, CNS inflammation,
but not axon loss, correlated with the degree of neurological disability.
In contrast, fixed neurological impairment
in chronic EAE correlated with axon loss that, in turn, correlated with
the number of symptomatic attacks.
As proposed for MS, these observations
imply a causal relationship between inflammation, axon loss, and irreversible
neurological disability.
This chronic-relapsing EAE model
provides an excellent platform for 2 critical objectives: investigating
mechanisms of axon loss and evaluating efficacy of neuroprotective therapies.
© Copyright by American Association
of Neuropathologists, Inc. 2002