Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization.
OBJECTIVE
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 degrees C, 34 degrees C, 31 degrees C, or 25 degrees C in halothane-anesthetized rats. The cortical DC voltage was recorded from a glass microelectrode while the cortical concentrations of glutamate, aspartate, glycine, and gamma-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 degrees C (mean +/- SD) to 294 +/- 34 seconds at 25 degrees 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 degrees C animals was 58.4 +/- 31.8 mumol/L; this decreased to 15.9 +/- 8.4 mumol/L at 25 degrees 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.
Nakashima
K
K
Department of Anesthesia, University of Iowa College of Medicine, Iowa City, USA.
Todd
M M
MM
D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001831:Body Temperature; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D004569:Electroencephalography; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006323:Heart Arrest; D007036:Hypothermia, Induced; D008297:Male; D008564:Membrane Potentials; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018846:Excitatory Amino Acids; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine