Features of astrocytic function apparently involved in the response of central nervous tissue to ischemia-hypoxia

Abstract

In this review I have tried to provide a framework for a comprehensive concept of the role(s) of astrocytes in energy metabolism and in ion homeostasis that might help to explain the reactions of astroglia to hypoxia-ischemia of the brain. The experimental basis for such a concept is still fragmentary, although advances have been made since this topic was last reviewed by the present author. This may be especially true with respect to the mechanism(s) of the potassium-induced swelling of astrocytes, which is likely to constitute at least one of the stimuli for the astrocytic swelling after hypoxia-ischemia. This review discusses whether this phenomenon may reflect an increased uptake of chloride together with sodium and/or potassium, occurring in exchange with the hydrogen and bicarbonate ions that result from the dissociation of carbonic acid and which might be a direct consequence of the enhancement of metabolic activity by elevated concentrations of potassium. One might, however, speculate whether a net uptake of ions must invariably be accompanied by fluid uptake (swelling) or whether the astrocytic cell membrane might occasionally be impermeable to water, a situation known to exist in the medulla of the kidney. If so, there would obviously be an increase in cellular osmolality, and the ability of astrocytes to maintain their respiratory activity during exposure to media of increased osmolality might suggest that such conditions do occur. A situation in which astrocytes carry out their functions in the face of excess extracellular potassium might provide a prime stimulus for the development of the alleged intracellular hyperosmolality. This is exactly the situation in ischemia, and such a mechanism could be the reason for the increase in brain osmolality described by Hossmann (1980) as a consequence of ischemia. In that case, the hyperosmolality would be brought about by ion redistribution and removal of water (probably to the venous side of the vascular system) and not by any additional solutes, which is in keeping with the observation of normal contents of all solutes studied (Hossmann, 1980). Although such a mechanism might be the major cause for astrocytic swelling and/or hyperosmolality, it should be kept in mind that the ability of cultured astrocytes to accumulate potassium very efficiently in a process catalyzed by Na+, K+-ATPase now seems to be well established. The precise correlations among the potassium-induced stimulation of oxygen uptake, the activity of Na+, K+-ATPase, and potassium uptake rates are, however, unclear. What also remains uncertain is the relative importance of astrocytic and neuronal potassium uptake in the brain in vivo and the mechanisms involved in the transfer to neurons of potassium which has initially been accumulated into astrocytes.