Figure 8: Summary diagram of the proposed mechanisms underlying progressive lesions in vascular dementia and the benificial effects of E2 administration during the first 3 months of BCCAO.

The rats underwent BCCAO 3 m exhibit memory decline, which is caused by axonal damage, reduction in hippocampal spine density and synaptic proteins. E2 administration for 3 m reduces these key pathogenic events, and further to underlie the later beneficial effects on preventing apoptosis and dementia-related protein expression, as well as preservation of cognitive function observed at 6 months after BCCAO in E2-treated animals.