Background and Purpose The effects of ischemia on the cerebral white m
atter structure seldom have been studied, possibly because white matte
r is generally considered less vulnerable to ischemia than gray matter
. The objective of this study was to evaluate the early (less than or
equal to 24 hours) structural effects of experimental focal ischemia o
n the cerebral white matter of the rat as a preliminary step to invest
igating human conditions of unknown pathogenesis that are characterize
d 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 lig
ht and electron microscopic methods, and the abnormalities were quanti
fied with an image-analysis system. Results As early as 30 minutes aft
er the arterial occlusion, there was conspicuous swelling of oligodend
rocytes and astrocytes; after 3 hours, large numbers of oligodendrocyt
es were lethally injured. These changes preceded by several hours the
appearance of necrotic neurons in the cortex and basal ganglia. Vacuol
ation and pallor of the white matter were very marked after 24 hours a
nd 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 chang
es in oligodendrocytes and myelinated axons appear early and seem to b
e concomitant with, but independent of, neuronal perikaryal injury. Mo
difications of this experimental model of focal ischemia could provide
the means to test the hypothesis that selected types of human leukoen
cephalopathies have an ischemic origin.