GPER1 inhibits nuclear factor kappa beta (NF-κB) and its target genes (e.g., TNFα and IL-1β) that lead to neuroprotection in rats with cerebral ischemia.152 In addition, activated GPER1 via estrogen can improve the function of tight junctions, and reduce the permeability of the blood-brain barrier.153 The timing and dose of estrogen therapy are really important for achieving the required neuroprotective effects.154 Neuroinflammation parameters that increase in ovariectomized mice hippocampus, like microglia activation and NF-κB, are also estimated for discovering mood disorders.155. This evidence concerns the gene GPER1 and brain ischemia.