Nissl staining showed the morphologic changes of neurons in the ischemic penumbra after MCAO. (A) Representative photographs showing neuronal damage in the ischemic penumbra after MCAO. (B) The number of injured neurons in the OVX group was significantly more than that in the control group (**p < 0.01). Treatment with 6 μg/kg or 20 μg/kg E2 significantly reduced neuronal damage and preserved morphology (#p < 0.05, v.s. OVX group). However, treatment with 50 μg/kg E2 significantly induced neuronal damage (**p < 0.05 v.s. the control group and 6 μg/kg or 20 μg/kg E2 replacement group). Scale bar: 20 μm.