White Matter Pathophysiology

Stroke is one of the most life-threatening diseases in most countries and is a leading cause of disability in the United States. Most ischemic strokes involve both white matter and gray matter, and 20% of strokes occur predominantly in white matter. The anatomy and physiology of white matter are different compared to gray matter, and the mechanisms of white matter stroke are less understood. Axons with their myelin and myelinating oligodendrocytes are the cell types that are most vulnerable to ischemic injury. In this chapter, we summarize and describe cellular and molecular mechanisms of axon-oligodendrocyte interactions and damage after ischemic stress. Then, we discuss potential therapeutic approaches to protect white matter and to promote white-matter repair after stroke in young and aging white matter. Understanding the different pathophysiologies of white matter and gray matter after stroke will guide us in developing meaningful comprehensive stroke therapies.