Mechanisms of demyelination and remyelination in the young and aged brain following white matter stroke

Subcortical white matter stroke (WMS) accounts for 25% of all incidences of stroke and results in severe motor and cognitive disability. WMS stands as the second leading cause of dementia and is immensely prevalent in older adults. In a startlingly statistic, a majority of human beings will present WMS by 80 years of age. Early ischemic lesions produced by WMS are asymptomatic and termed “silent strokes”. WMS is, however, progressive with both the size of the lesions and their distribution, increasing as patients age. Pathological analyses in both postmortem human tissue samples and mouse models of WMS demonstrate myelin degeneration as a chief hallmark of WMS. This suggests that the development of rehabilitative strategies in human WMS will necessitate an understanding of the pathophysiology of demyelination and remyelination following ischemic injury. This review will address our current understanding of WMS from human imaging studies, the development of rodent models of WMS, the mechanistic underpinning of myelin degeneration following WMS as well as remyelination dynamics in the adult brain.