Mechanisms and Patterns of Axonal Loss in Multiple Sclerosis

Abstract

After a variable or silent initial course, MS patients often enter a progressive neurological decline leading to permanent clinical disability. Axonal loss is considered the major factor behind this process. Elucidating the etiology and pathogenesis of this phenomenon is critical to developing treatments for progressive MS. Here we discuss pathologic presentation of axonal loss in MS, patterns of axonal loss at certain disease stages, and evidence that axonal loss in MS progresses independently of clinical relapses but coincides strongly with inflammation. Mechanisms behind axonal loss in MS include T cell attack, reactive nitrogen species-induced damage, loss of myelin (demyelination), and loss of trophic support from oligodendrocytes. Also, we will review animal models of neurodegeneration that share similar disease features with MS axonopathy. Finally, we will consider the progress of therapeutic strategies aimed at axonal preservation in MS including remyelination enhancement, blockage of Na+ channels and prevention of free radical formation.