Axonal Loss in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) lesions are characterized by inflammation, demyelination, loss of oligodendrocytes, reactive astrogliosis, and axonal injury. Traditionally, inflammation and demyelination have been emphasized as the two major pathological events in MS. Accordingly, MS research has focused on damage to oligodendrocytes and myelin, and on the roles of T-cells and macrophages, during demyelination. In contrast, axonal injury in MS has received less attention both clinically and in research. Axonal pathology, however, has been recognized as a part of MS pathology for more than a century [1]. Charcot, for example, described MS lesions in terms of demyelination and a relative sparing of axons [2]. Recently, the identification of primary axonal pathology in mice with myelin protein gene mutations, pathological evidence for axonal loss in MS brains, and magnetic resonance imaging (MRI) evidence of changes in MS brains, have generated new focus on the role of axons in the pathogenesis of MS. It is now generally accepted that axonal loss plays an important role in the irreversible functional decline experienced by many MS patients [3–8]. This chapter discusses current knowledge regarding the extent, timing, and clinical significance of axonal damage in the pathogenesis of MS.