Stroke in CNS white matter: Models and mechanisms

White matter stroke (WMS) is a debilitating disorder, which is characterized by the formation of ischemic lesions along subcortical white matter tracts of the central nervous system. Initial infarction during the early stages of the disease is often asymptomatic and is thus considered a form of silent stroke. However, over time lesions accumulate, resulting in severe cognitive and motor decline of which there are no known therapies. Functional imaging and post mortem analysis of patients demonstrates a loss of oligodendrocytes and the subsequent damage of myelin as a primary hallmark of WMS lesions. Though the adult mammalian brain maintains the capacity to regenerate adult oligodendrocytes, this process is blocked in the infarcted white matter thereby preventing remyelination. Recent evidence suggests that activation of neural circuits via motor training or direct stimulation drives oligodendrogenesis and de novo myelin synthesis, opening a potential avenue for therapy in WMS.