ERα has been implicated as particularly important in the neuroprotective effects of E2, as evidenced by the fact that E2-mediated neuroprotection against middle cerebral artery occlusion (MCAO)-induced cerebral ischemia is lost in OVX ERα knockout mice, but not ERβ-KO mice [13], [14], and by the fact that ERα, but not ERβ, antisense oligonucleotides significantly attenuate E2 neuroprotection in the hippocampal CA1 region following global cerebral ischemia (GCI) [15]. Here, ESR1 is linked to brain ischemia.