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 17ß-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 α (ERα) and ß (ERß), 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.

Effect of retinoic acid on the neurovascular unit: A review.

Retinoic acid is a metabolic product derived from vitamin A, acting at a nuclear level to maintain the proper transcriptional activity. Moreover, this molecule contributes to the development and maturation of the cerebral vascular system, playing a pivotal role in development and maintenance of neurovascular unit integrity. This physiological structure is comprised of glial cells, vascular cells, and neurons, ensuring the correct function of the blood-brain barrier and, at last instance, the homeostasis of the central nervous system. Therefore, retinoic acid ensures the physiological structure integrity of the neurovascular unit, decreasing the development of neurological disorders. Furthermore, retinoic acid can modulate the physiological function of the neurovascular unit cells, which is crucial to the maintenance of this physiological structure. The deletion of this molecule leads to the development of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease. In addition, impaired signaling of this molecule contributes to a worse prognosis in the recovery after ischemic stroke. This review characterizes the cellular components that constitute the neurovascular unit and analyzes the effect of retinoic acid on these cellular components that, in a coordinated manner, are responsible for homeostasis of the central nervous system. Through this description, it seems apparent that retinoic acid administration might be an essential pharmacological tool in the near future.