Pathophysiology of Ischemic White Matter Injury

Cerebral white matter is sensitive to ischemic injury at all developmental ages. For ischemic stroke, the extent of white matter injury is an important predictor of long-term functional outcome. White matter is comprised of myelinated and unmyelinated axons, glial cells, and blood vessels. Understanding the unique pathophysiology of white matter injury requires recognition of ischemic vulnerability of the individual cellular components, as well as their interactions. In this review we focus on several well-established injury pathways: ionic imbalance, leading to toxic calcium accumulation within axons; glutamate excitotoxicity targeted to oligodendrocytes and myelin; and autodestructive mechanisms activated by axon damage. Knowledge of these complex and interlinked processes presents opportunities to direct neuroprotective and repair strategies specifically to white matter, improving functional recovery after stroke.