Background and Purpose: Hypothermia slows the increase in extracellular excitatory amino acid (EAA) concentrations during temporary cerebral ischemia. However, it is unclear whether hypothermia slows the rate of EAA release or just delays the time until the first sharp increase (which occurs coincident with terminal depolarization). Methods: Pericranial temperatures were adjusted to 38°C, 24°C, 31°C, or 25°C in halothane-anesthetized rats. The cortical CD voltage was recorded from a glass microelectrode while the cortical concentrations of glutamate, aspartate, glycine, and γ- aminobutyric acid (GABA) were measured by microdialysis. A cardiac arrest was induced with intravenous KCl, and the times until electroencephalograph isoelectricity and terminal depolarization were recorded. Dialysate concentrations of the four compounds were measured at 10, 20, and 30 minutes after depolarization. Results: The times to isoelectricity and depolarization varied inversely with temperature; depolarization time increased from 70±9 seconds at 38°C (mean±SD) to 294±34 seconds at 25°C. The dialysate concentrations of all four compounds increased during ischemia, and the rate of increase was inhibited by cooling. After 30 minutes of ischemia, glutamate concentration in 38°C animals was 58.4±31.8 μmol/L; this decreased to 15.9±8.4 μmol/L at 25°C. The magnitude of the effects of temperature on amino acid release differed with the compound measured. For glutamate, the calculated Q10 was 3.63. Corresponding values for aspartate and glycine were 3.68 and 1.95, respectively. By contrast, Q10 for GABA release was 6.31, indicating greater sensitivity to cooling. Conclusions: These results suggest that effects of hypothermia on EAA concentrations during cerebral ischemia may be the result of both a delay until initial EAA release as well as a direct effect of temperature on the rate of amino acid release. The observed temperature effects are more consistent with carrier-mediated processes controlling EAA release.
- cerebral ischemia, global
- excitatory amino acids