The spectrum of Ischemia-induced white matter injury varies with age

Abstract

Stroke is a neurological condition that targets the whole range of the human population, from the pre-term infant to the elderly and is a major cause of death worldwide (Ingall 2004). During its lifespan, the brain's vulnerability to hypoxia-ischemia varies. Term infants who suffer this insult usually exhibit widespread neuronal injury in the cerebral cortex with a stroke-like distribution of damage (Deng 2008), whereas in pre-term infants immature oligodendrocytes and subplate neurons below the neocortex are most vulnerable and result in Periventricular Leukomalacia (PVL) (Back et al. 2007; McQuillen et al. 2005). The incidence of stroke decreases in young adulthood, but peaks again in the elderly. Moreover, the underlying pathological mechanisms that occur following ischemia are different at each stage.

Experimental stroke research on stroke has traditionally focused on grey matter injury, but recent evidence indicates that white matter injury is a critical part of its pathophysiology. In this debilitating condition the mechanisms of ischemia-induced damage differ with age and all cellular components of white matter (axons, oligodendrocytes and astrocytes) are affected.

This review paper focuses on the relative vulnerability to ischemia of white matter during the course of development and on our recent findings of how individual cellular components are affected during each stage.