As shown in Fig. 2, work by our laboratory showed that NADPH oxidase activity increases rapidly in the hippocampal CA1 region following GCI in ovariectomized female rats, with peak levels observed at 3h after reperfusion (42). Note that the pattern of NADPH oxidase activation following cerebral ischemia is similar to that we observed for O2- elevation. As also shown in Fig. 2, E2 treatment strongly attenuated the elevation of NADPH oxidase activity in the hippocampal CA1 region following cerebral ischemia, which correlated with its suppression of O2- levels and its neuroprotective effect (42).