Worldwide ischemia promotes cleavage of the biologically inactive precursor procaspase 3 to generate activated caspase 3, ischemiainduced caspase 3 activity is maximum at 24 h after insult. To directly measure caspase 3 like useful activity after ischemia, brain sections were labeled by us with FAM DEVD FMK, a fluorescein tagged analog of the caspase inhibitor zDEVD FMK, at 2-4 h. FAM DEVD FMK enters cells order Clindamycin and binds irreversibly to catalytically active caspase 3, and hence offers a fluorescent indicator of the abundance of active caspase 3. In brain sections from control animals, caspase activity was low. International ischemia induced a 16 fold increase in activity in the hippocampal CA1, apparent at 2-4 h. The escalation in activity was subfieldspecific because it was not seen in the CA3 or dentate gyrus. Intense estradiol cure blocked the ischemiainduced peak of caspase 3 activity in CA1. These studies provide clear evidence implicating the Akt pathway as a crucial mobile mediator of the neuroprotection afforded by a dose of estradiol given at the onset of reperfusion in a clinically relevant model of global ischemia. We now have evidence that icv administration of a much lower dose is equally as effective as the large dose and that LY294002 also blocks safety from the low dose. These answers are in agreement with findings of others that Akt is critical to cell survival after Mitochondrion cerebral ischemia and show that hormone administration after an ischemic event may keep Akt signaling. Activation of suppression and Akt of GSK3B mediates neuroprotection of vulnerable hippocampal CA1 neurons after transient worldwide ischemia by overexpression of copper/zincsuperoxide dismutase or by ischemic preconditioning. Estradiol acts via PI3K to afford protection of cultured cortical neurons subjected to chemically induced death and of neurons in organotypically cultured hippocampal slices subjected to oxygen?glucose starvation. PI3K/Akt signaling participates in the actions of estradiol pretreatment in gerbils afflicted by focal ischemia. Wenowdocument the participation of Akt in the neuroprotection afforded with a simple, acute injection of estradiol provided at the time of reperfusion in a clinically relevant model of global ischemia in rats. Our results purchase Pemirolast are consistent with the hypothesis that a large dose of estradiol used soon after induction of world wide ischemia functions via PI3K/Akt signaling to advertise survival of post ischemic neurons. Government of the PI3K inhibitor LY294002 blocks the ability of estradiol to promote survival of CA1 pyramidal neurons in the post ischemic hippocampus.