Non-genomic Effect of Estradiol on the Neurovascular Unit and Possible Involvement in the Cerebral Vascular Accident

Cerebrovascular diseases, such as ischemic cerebral vascular accident (CVA), are responsible for causing high rates of morbidity, mortality, and disability in the population. The neurovascular unit (NVU) during and after ischemic CVA plays crucial roles in cell regulation and preservation, the immune and inflammatory response, and cell and/or tissue survival and repair. Cellular responses to 17 beta-estradiol (E2) can be triggered by two mechanisms: one called classical or genomic, which is due to the activation of the classical nuclear estrogen receptors alpha (ER alpha) and beta (ER beta), and the non-genomic or rapid mechanism, which is due to the activation of the G protein-coupled estrogen receptor 1 (GPER) that is located in the plasma membrane and some in intracellular membranes, such as in the Golgi apparatus and endoplasmic reticulum. Nuclear receptors can regulate gene expression and cellular functions. On the contrary, activating the GPER by E2 and/or its G-1 agonist triggers several rapid cell signaling pathways. Therefore, E2 or its G-1 agonist, by mediating GPER activation and/or expression, can influence several NVU cell types. Most studies argue that the activation of the GPER may be used as a potential therapeutic target in various pathologies, such as CVA. Thus, with this review, we aimed to summarize the existing literature on the role of GPER mediated by E2 and/or its agonist G-1 in the physiology and pathophysiology of NVU.

Automated summary

Cerebrovascular diseases, such as ischemic CVA, have a significant impact on morbidity, mortality, and disability rates. The neurovascular unit (NVU) plays a crucial role in cell regulation and survival, inflammation, and tissue repair during and after ischemic CVA. Estrogen activation through nuclear estrogen receptors (ER alpha and ER beta) and G protein-coupled estrogen receptor 1 (GPER) has both genomic and non-genomic effects on cellular functions. Activation of GPER by estrogen or its agonist G-1 has been identified as a potential therapeutic target for various pathologies, including CVA. This review aims to summarize the literature on the role of GPER in NVU physiology and pathophysiology.