Demyelination and axonal damage in a non-human primate model of multiple sclerosis

The demyelinating plaque is the paradigmatic lesion of multiple sclerosis ( MS), but only recently attention has been given to axonal damage and to its role in the pathophysiology of disease. Albeit the possible relevance of a xonal loss in MS and its experimental models, the amount and timing of axon al sufferance has been addressed only in experimental autoimmune encephalom yelitis (EAE) of rodents. In this report we observed that, in the marmoset model of EAE, axonal damage occurs early during the demyelinating process a s assessed by immunoreactivity for amyloid precursor protein (APP) and non- phosphorylated neurofilaments (SMI-32 positive) detected mostly in early ac tive lesions compared to late active and normal appearing white matter. The rare occurrence of morphological features of axonal transection, such as A PP or SMI-32 positive spheroids and swellings, as well as an increase of ne urofilament density in the demyelinated axons without accumulation of elect ron dense organelles or osmiophilic bodies, at electron microscopy, suggest s that early axonal damage may be, at least in part, a reversible process. These findings are of relevance for the development of therapies, which can protect axons and enhance their function and survival. (C) 2001 Elsevier S cience B.V. All rights reserved.