ABSTRACT
Astrocytes have an essential role in supporting neuronal function by maintaining the normal composition of the extracellular milieu.1 By this clearance activity, astrocytes protect neurons from the potential injuring or the disturbing effects of excessive concentration of molecules such as glutamate, K+, ammonium, or lactate. Specific mechanisms of uptake or metabolism operate in astrocytes in optimal conditions to accomplish this homeostatic function. During the progress of pathologies such as ischemia, trauma, epilepsies, and hepatic encephalopathy, the clearance or metabolic capacities of astrocytes initially fulfill their protective role on neurons, but at the cost of altering their own homeostasis, including the increase in cell volume. If the pathological conditions persist or progress, the mechanisms of protection are overwhelmed and astrocytes not
only fail to restore the brain homeostasis, but also may trigger responses that exacerbate and spread the original damage. Astrocyte swelling may occur as consequence of a decrease in external osmolarity or in isosmotic conditions, by changes in ion redistribution, or accumulation of ammonia or lactate. This is called cytotoxic or cellular swelling.2 These two types of swelling are characteristically different from the vasogenic edema, in which the hallmark is the brain-blood barrier disruption. However, pathologies leading to brain edema are not, in general, entirely associated with one type of edema, as during the progress of the pathology the initially pure vasogenic edema gradually results in the development of cellular edema, just as much as cellular edema can induce blood-brain barrier disruption and enable the development of vasogenic edema. In the present review, the emphasis will be put recent findings about the molecular aspects of mechanisms leading to osmotic or cellular astrocyte swelling. Other issues addressed in this chapter include the reasons why astrocytes fail to efficiently operate mechanisms of cell volume correction during cellular swelling and the consequences of astrocyte swelling in the pathology evolution. The consistent observation of a preferential swelling of astrocytes over neurons is discussed in light of the mechanisms operating in each type of cell in response to the swellinggenerating factors.
