Multiple sclerosis and chronic autoimmune encephalomyelitis - A comparative quantitative study of axonal injury in active, inactive, and remyelinatedlesions

Recent magnetic resonance (MR) studies of multiple sclerosis lesions indica te that axonal injury is a major correlate of permanent clinical deficit. I n the present study we systematically quantified acute axonal injury, defin ed by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neu rites, in the central nervous system of 22 multiple sclerosis patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic auto immune encephalomyelitis (EAE), The highest incidence of acute axonal injur y was found during active demyelination, which was associated with axonal d amage in periplaque and in the normal appearing white matter of actively de myelinating cases. In addition, low but significant axonal injury was also observed in attractive demyelinated plaques. In contrast, no significant ax onal damage was found in remyelinated shadow plaques. The patterns of axona l pathology in chronic active EAE were qualitatively and quantitatively sim ilar to those found in multiple sclerosis, Our studies confirm previous obs ervations of axonal destruction in multiple sclerosis lesions during active demyelination, but also indicate that ongoing axonal damage in inactive le sions may significantly contribute to the clinical progression of the disea se. The results further emphasize that MOG-induced EAE may serve as a suita ble model for testing axon-protective therapies in inflammatory demyelinati ng conditions.