Astroglial Modulation of Hydromineral Balance and Cerebral Edema

Maintenance of hydromineral balance (HB) is an essential condition for life activity at cellular, tissue, organ and system levels. This activity has been considered as a function of the osmotic regulatory system that focuses on hypothalamic vasopressin (VP) neurons, which can reflexively release VP into the brain and blood to meet the demand of HB. Recently, astrocytes have emerged as an essential component of the osmotic regulatory system in addition to functioning as a regulator of the HB at cellular and tissue levels. Astrocytes express all the components of osmoreceptors, including aquaporins, molecules of the extracellular matrix, integrins and transient receptor potential channels, with an operational dynamic range allowing them to detect and respond to osmotic changes, perhaps more efficiently than neurons. The resultant responses, i.e., astroglial morphological and functional plasticity in the supraoptic and paraventricular nuclei, can be conveyed, physically and chemically, to adjacent VP neurons, thereby influencing HB at the system level. In addition, astrocytes, particularly those in the circumventricular organs, are involved not only in VP-mediated osmotic regulation, but also in regulation of other osmolality-modulating hormones, including natriuretic peptides and angiotensin. Thus, astrocytes play a role in local/brain and systemic HB. The adaptive astrocytic reactions to osmotic challenges are associated with signaling events related to the expression of glial fibrillary acidic protein and aquaporin 4 to promote cell survival and repair. However, prolonged osmotic stress can initiate inflammatory and apoptotic signaling processes, leading to glial dysfunction and a variety of brain diseases. Among many diseases of brain injury and hydromineral disorders, cytotoxic and osmotic cerebral edemas are the most common pathological manifestation. Hyponatremia is the most common cause of osmotic cerebral edema. Overly fast correction of hyponatremia could lead to central pontine myelinolysis. Ischemic stroke exemplifies cytotoxic cerebral edema. In this review, we summarize and analyze the osmosensory functions of astrocytes and their implications in cerebral edema.