Cerebral White Matter Is Highly Vulnerable to Ischemia

Background and Purpose The effects of ischemia on the cerebral white matter structure seldom have been studied, possibly because white matter is generally considered less vulnerable to ischemia than gray matter. The objective of this study was to evaluate the early (≤24 hours) structural effects of experimental focal ischemia on the cerebral white matter of the rat as a preliminary step to investigating human conditions of unknown pathogenesis that are characterized by selective damage to the white matter. Methods Twenty-eight rats, including four controls, had a middle cerebral artery occluded with an intravascular filament for periods ranging between 0.5 and 24 hours. Brain samples from the subcortical white matter were examined with light and electron microscopic methods, and the abnormalities were quantified with an image-analysis system. Results As early as 30 minutes after the arterial occlusion, there was conspicuous swelling of oligodendrocytes and astrocytes; after 3 hours, large numbers of oligodendrocytes were lethally injured. These changes preceded by several hours the appearance of necrotic neurons in the cortex and basal ganglia. Vacuolation and pallor of the white matter were very marked after 24 hours and reflected the segmental swelling of myelinated axons, the formation of spaces between myelin sheaths and axolemma, and astrocyte swelling. Conclusions These results suggest that the cerebral white matter is highly vulnerable to the effects of focal ischemia. Pathological changes in oligodendrocytes and myelinated axons appear early and seem to be concomitant with, but independent of, neuronal perikaryal injury. Modifications of this experimental model of focal ischemia could provide the means to test the hypothesis that selected types of human leukoencephalopathies have an ischemic origin.