Glutamate receptors and white matter stroke

White matter (WM) damage during ischemia occurs at multiple sites including myelin, oligodendrocytes, astrocytes and axons. A major driver of WM demise is excitoxicity as a consequence of excessive glutamate release by vesicular and non-vesicular mechanisms from axons and glial cells. This results in over-activation of ionotropic glutamate receptors (GluRs) profusely expressed by all cell compartments in WM. Thus, blocking excitotoxicity in WM with selective antagonists of those receptors has a potential therapeutic value. The significance of WM GluR expression for WM stroke injury is the focus of this review, and we will examine the role of GluRs in injury to myelin, oligodendrocytes, astrocytes and the axon cylinder.