Calcium dyshomeostasis in astrocytes after ischemia

Abstract

Astrocytes play significant roles in the demise of brain tissue after cerebral ischemia. Dysfunction in the Ca2+ homeostasis process has the potential to contribute to cellular damage in ischemia through loss of astrocytic normal functions or through gain of detrimental effects. In this chapter, we summarize the role of astrocyte Ca2+ signaling in physiology and pathophysiolgy of brain ischemia, their different modes of initiation, and their functional significance for astrocytes and astrocyte-neuron communication. In particular, we review current knowledge about the independent intrinsic Ca2+ activity of astrocytes and how these cells respond with Ca2+ elevations in their cytosol to synaptic activity. Both forms of astrocyte Ca2+ increases are produced predominantly by Ca2+ release from IP3 receptor-mediated intracellular stores. Astrocyte Ca2+ elevations are coupled to regulated release of gliotransmitters, including glutamate, adenosine 5 ' triphosphate (ATP), or D-serine, which modulate synaptic activity in adjacent neurons. In turn, astrocytes release vasoactive compounds that regulate cerebrovasculature. Changes in astrocytic Ca2+ signaling during ischemia and reperfusion may contribute to aberrant astrocyte metabolism and release of gliotransmitters, which may result in brain edema and altered activity of gap junctions. Modulating astrocytic Ca2+ signaling may help to develop new therapeutic means to diminish brain damage after stroke.