Nakashima K, Todd M M
Department of Anesthesia, University of Iowa College of Medicine, Iowa City, USA.
Stroke. 1996 May;27(5):913-8. doi: 10.1161/01.str.27.5.913.
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).
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.
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.
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.
低温可减缓短暂性脑缺血期间细胞外兴奋性氨基酸（EAA）浓度的升高。然而，尚不清楚低温是减缓了EAA的释放速率，还是仅仅延迟了首次急剧升高（与终末期去极化同时发生）的时间。
在氟烷麻醉的大鼠中，将颅周温度调节至38℃、34℃、31℃或25℃。用玻璃微电极记录皮质直流电压，同时通过微透析测量皮质中谷氨酸、天冬氨酸、甘氨酸和γ-氨基丁酸（GABA）的浓度。静脉注射氯化钾诱发心脏骤停，并记录脑电图等电位和终末期去极化的时间。在去极化后10、20和30分钟测量四种化合物的透析液浓度。
等电位和去极化时间与温度呈反比；去极化时间从38℃时的70±9秒增加到25℃时的294±34秒。缺血期间所有四种化合物的透析液浓度均升高，且冷却可抑制升高速率。缺血30分钟后，38℃组动物的谷氨酸浓度为58.4±31.8μmol/L；在25℃时降至15.9±8.4μmol/L。温度对氨基酸释放的影响程度因所测化合物而异。对于谷氨酸，计算得出的Q10为3.63。天冬氨酸和甘氨酸的相应值分别为3.68和1.95。相比之下，GABA释放的Q10为6.31，表明对冷却更敏感。
这些结果表明，低温对脑缺血期间EAA浓度的影响可能是延迟初始EAA释放以及温度对氨基酸释放速率直接作用的结果。观察到的温度效应与控制EAA释放的载体介导过程更为一致。
