Neuroprotective actions of estradiol and novel estrogen analogs in ischemia: Translational implications

► Estradiol pretreatment attenuates ischemia-induced death of hippocampal neurons. ► Estradiol given immediately after ischemia is highly neuroprotective. ► Estradiol treatment improves cognitive outcomes after global ischemia. ► Estrogens retain their neuroprotective efficacy in hormone-withdrawn older females. ► The transcription factor CREB may be a downstream mediator of estradiol protection.