Effect of Superoxide Dismutase on Intracellular Calcium in Stroke

Abstract

To clarify the relationship between calcium metabolism and free radical damage during the reperfusion period following ischemia, we investigated the effect of superoxide dismutase (SOD) on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 12 cats. Using indo-1, a fluorescent intracellular Ca²⁺ indicator, we simultaneously measured changes in the Ca²⁺ signal ratio (400:500 nm), NADH signal (464 nm), and reflectance (340 nm) during ultraviolet excitation (340 nm) directly from the cortex in vivo. The middle cerebral artery (MCA) was occluded for 1 h; only cats in which the EEG amplitude was depressed to 2+ signal ratio increased significantly in both groups with no significant difference between the groups. During reperfusion, the Ca²⁺ signal ratio remained at a high level in the vehicle-treated group, while in the SOD-treated group, the Ca²⁺ signal ratio decreased. There was a statistically significant difference between the two groups at 10, 20, and 30 min after reperfusion (p < 0.01). The histologically damaged area in the SOD-treated group was significantly smaller than that in the vehicle-treated group (p < 0.01). These data suggest that the histoprotective action of SOD may be due to its ability to attenuate increases in intracellular calcium during the recirculation period following focal cerebral ischemia.