To verify whether lipid peroxidation is associated with focal
cerebral ischemia, a unilateral
middle cerebral artery occlusion was carried out in rats. The concentrations of various
endogenous antioxidants in the ischemic center were measured, including
alpha-tocopherol and ubiquinones as
lipid-soluble
antioxidants and ascorbate as a water-soluble
antioxidant. At 30 minutes after
ischemia,
alpha-tocopherol decreased to 79% of baseline, reduced
ubiquinone-9 to 73%, ubiquinone-10 to 66%, and reduced ascorbate to 76%. Six hours after
ischemia,
alpha-tocopherol decreased to 63% and reached a plateau, whereas reduced ubiquinones and reduced ascorbate declined further to 16% and 10%, respectively, 12 hours after
ischemia and then reached plateau levels. These results suggest functional and durational differences between
antioxidants and lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during
ischemia was not observed, that of oxidized ascorbate was noted. The complementary
antioxidant system between cytoplasmic and membranous components, the combination
alpha-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these
antioxidants on the basis that the loss of these reduced
antioxidants is due to neutralization of
free radicals. This system is suggested to play an important role in the early ischemic period.
Urate also increased during
ischemia. The possible involvement of the
xanthine-
xanthine oxidase system in initiating
free radical reactions in
cerebral ischemia is also discussed.