|
pubmed:abstractText |
Nearly complete brain ischemia under normoglycemic conditions results in death of only selectively vulnerable neurons. With prior elevation of brain glucose, such injury is enhanced to include pancellular necrosis (i.e., infarction), perhaps because an associated, severe lactic acidosis preferentially injures astrocytes. However, no direct physiologic measurements exist to support this hypothesis. Therefore, we used microelectrodes to measure intracellular pH and passive electrical properties of cortical astrocytes as a first approach to characterizing the physiologic behavior of these cells during hyperglycemic and complete ischemia, conditions that produce infarction in reperfused brain. Anesthesized rats (n = 26) were made extremely hyperglycemic (blood glucose, 51.4 +/- 2.8 mM) so as to create potentially the most extreme acidic conditions possible; then ischemia was induced by cardiac arrest. Two loci more acidic than the interstitial space (6.17-6.20 pH) were found. The more acidic locus [4.30 +/- 0.19 (n = 5); range: 3.82-4.89] was occasionally seen at the onset of anoxic depolarization, 3-7 min after cardiac arrest. The less acidic locus [5.30 +/- 0.07 (n = 53); range 4.46-5.93)] was seen 5-46 min after cardiac arrest. A small negative change in DC potential [8 +/- 1 mV (n = 5); range -3 to -12 mV and 7 +/- 2 mV (n = 53); range +3 to -31 mV, respectively] was always seen upon impalement of acidic loci, suggesting cellular penetration. In a separate group of five animals, electrical characteristics of these cells were specifically measured (n = 17): membrane potential was -12 +/- 0.2 mV (range -3 to -24 mV), input resistance was 114 +/- 16 M omega (range 25-250 M omega), and time constant was 4.4 +/- 0.4 ms (range 3.0-7.9 ms). Injection of horseradish peroxidase into cells from either animal group uniformly stained degenerating astrocytes. These findings establish previously unrecognized properties of ischemic astrocytes that may be prerequisites for infarction from nearly complete ischemia: the capacity to develop profound cellular acidosis and a concomitant reduction in cell membrane ion permeability.
|
