Figure 8. A proposed model.

Upon OGD/reperfusion injury (+OGD), NF-κB p65 translocates into the nucleus (Supplemental Figure 4). In turn, activated NF-κB p65 binds to MMP gene promoters thereby stimulates MMP gene expression in bEnd.3 cells. This event results in the degradation of tight junction proteins and BBB disruption (31, 49, 50). However, E₂ treatment (+OGD/+E₂) induces nuclear translocation of ERα and association of ERα with NF-κB p65 and N-CoR corepressor, which leads to the down-regulation of MMP gene expression. Therefore, E₂ has a protective effect on the BBB disruption via preservation of tight junction proteins.