Estradiol prevents ischemia-induced dephosphorylation of CREB in CA1 cell nuclei 3 h after global ischemia in OVX rats. Representative Western blots (A) and relative abundance (B and C) of p-CREB and CREB in the nuclear fraction of CA1 of placebo and estradiol (E) treated rats subjected to sham surgery or ischemia (isx) at 3 h after reperfusion. Data are expressed relative to controls (young sham) (B and C). Irrespective of age and E treatment, ischemia induced dephosphorylation of CREB (B) (P < 0.01 vs sham). Estradiol prevented the decrease in nuclear p-CREB in young and middle-aged ischemic rats (D; P < 0.05 vs all ischemic rats). Overall, middle-aged rats had lower p-CREB in the CA1 than young rats (E; P < 0.05 all young groups vs all middle-aged groups). No differences were found in total CREB (C). *, ** P < 0.05, P < 0.01, respectively.