New light on white matter.

Injury of central white matter is a major cause of functional disability in cerebrovascular disease. White matter is a target of hypoxic-ischemic injury throughout life, in clinical settings ranging from periventricular leukomalacia in the neonatal period, stroke and cardiac arrest in adults, to vascular dementia in the aging brain. The traditional view from animal studies is that gray matter is more vulnerable than white matter to ischemia.1 In part, this view may be an artifact of how ischemic brain injury has been studied. Most experimental work has used rodents, in which white matter constitutes only about 14% of total brain volume; in man, white matter is about 50% of brain volume.2 In fact, the metabolic rate of white matter is only modestly lower than that of gray matter,3 and recent animal studies suggest that white matter can be damaged even by brief ischemia.4 Moreover, clinical experience teaches that human ischemic stroke is almost never confined to gray matter. White matter is damaged by infarction in the territory of small vessels which perfuse centrum semiovale and deeper fiber pathways, and it is also damaged by occlusion of the large intracranial arteries which supply superficial gray and white matter together. Disruption of central conduction pathways may cause disruption of motor and sensory function, neurobehavioral syndromes,5 and cognitive impairment.6,7 Lacking neuronal cell bodies, dendrites, or synapses, white matter is unlikely to be injured by many of the mechanisms defined specifically in gray matter. Along with growing recognition of the importance of white matter ischemia in clinical disease, there have been recent advances in white matter pathophysiology, pharmacology, and imaging.