A, C, 17β-Estradiol reduces tau hyperphosphorylation after global cerebral ischemia as determined by Western blot analysis with PHF-1 antibodies. Values are mean ± SEM of determinations from five to six individual rats, and expressed as fold change versus sham control. Pla, Placebo; R, reperfusion. Ba–Bf, DAB immunostaining showing tau hyperphosphorylation at 24 h after global cerebral ischemia in hippocampus CA1 and attenuation by E2. Results are representative of staining observed in five individual animals per group (magnification, 40×). Scale bar, 50 μm. D, E, Administration of the JNK inhibitor SP600125 abolishes global cerebral ischemia-induced tau hyperphosphorylation at 24 h after global cerebral ischemia. Values are means ± SEM of determinations from five to six individual rats expressed as fold change versus sham control. *p < 0.05 versus sham control, #
p < 0.05 versus Pla group at the same time point. F, Administration of the JNK inhibitor SP600125 significantly attenuated hippocampal CA1 neuronal cell death as measured by counting of NeuN-positive cells at 7 d after global cerebral ischemia. Representative NeuN staining in hippocampus CA1 from vehicle- and SP600125-treated rats is shown in the inset. Values are mean ± SEM of determinations from five to six individual rats. #
p < 0.01 versus vehicle and placebo.