Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions.
Recent magnetic resonance (MR) studies of multiple sclerosis lesions indicate that axonal injury is a major correlate of permanent clinical deficit. In the present study we systematically quantified acute axonal injury, defined by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in the central nervous system of 22 multiple sclerosis patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune encephalomyelitis (EAE). The highest incidence of acute axonal injury was found during active demyelination, which was associated with axonal damage in periplaque and in the normal appearing white matter of actively demyelinating cases. In addition, low but significant axonal injury was also observed in inactive demyelinated plaques. In contrast, no significant axonal damage was found in remyelinated shadow plaques. The patterns of axonal pathology in chronic active EAE were qualitatively and quantitatively similar to those found in multiple sclerosis. Our studies confirm previous observations of axonal destruction in multiple sclerosis lesions during active demyelination, but also indicate that ongoing axonal damage in inactive lesions may significantly contribute to the clinical progression of the disease. The results further emphasize that MOG-induced EAE may serve as a suitable model for testing axon-protective therapies in inflammatory demyelinating conditions.
Kornek
B
B
Division of Neuroimmunology, Brain Research Institute, University of Vienna, Austria.
Storch
M K
MK
Weissert
R
R
Wallstroem
E
E
Stefferl
A
A
Olsson
T
T
Linington
C
C
Schmidbauer
M
M
Lassmann
H
H
D000208:Acute Disease; D000328:Adult; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D009186:Myelin Sheath / Q000737:chemistry / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew
D016564:Amyloid beta-Protein Precursor