Astrocytic H + and Ca 2+ Changes: Implications for Ischemic Brain Injury

Astrocytes closely interact with all other brain cell elements. Therefore the consequences of brain injury from ischemia may be reflected specifically in the behavior of these cells. Astrocytes are either transformed into so–called “reactive species” after a reduction in blood flow [1, 33], or they are destroyed by the process, along with other brain cell elements [1]. Reactive astrocytosis is a process that may influence mechanisms by which the brain develops [28], functions under normal circumstances, and responds to global ischemia with selective loss of vulnerable neurons [18]. Alternatively, destruction of astrocytes from ischemia may not only contribute to selective loss of vulnerable neurons but also play a key role in the development of brain infarction [20, 23]. Two well–conserved and essential physiologic processes of eukaryotic cells that sensitively reflect their functional status are the regulation of intracellular pH (pHj) and calcium (Ca2+j) [6]. For example, a rise in pHj heralds the onset of increased cellular activity while a fall in pHi is associated with a reduction in vital processes in numerous cell types [5]. Furthermore, a rise in Ca2+i is a ubiquitous trigger for both constructive [41] and destructive cellular events [10, 11, 14, 36]. We are studying the role that astroglial changes in pHi and Ca2+i may have in causing the functional changes from ischemia that are seen in astrocytes.