Farooque M, Hillered L, Holtz A, Olsson Y
Laboratory of Neuropathology, University Hospital, Uppsala, Sweden.
J Neurotrauma. 1997 Jan;14(1):63-9. doi: 10.1089/neu.1997.14.63.
We evaluated in rats, the effect of moderate hypothermia (30-31 degrees C) on extracellular levels of amino acids, with special emphasis on the excitatory amino acids (EAAs) glutamate and aspartate, lactate and pyruvate, after severe spinal cord compression. A laminectomy of Th7 and Th8 was made. A probe was inserted in a dorsal horn and microdialysis was performed for 1.5 h before and 4 h after applying severe compression for 5 min. Dialysate samples were collected at intervals of 10 min and analyzed by high-performance liquid chromatography. In normothermic (37.5 degrees C) animals there was a several-fold rise of glutamate that peaked in the first 10 min fraction after trauma. Hypothermic animals showed a similar increase after trauma, which was statistically significant until 20 min after injury. The level of glutamate was significantly higher in hypothermic animals from 20 to 70 min after injury, compared with normothermic animals. Aspartate also showed a marked increase following injury. The peak concentration was similar for both groups, whereas recovery was delayed in hypothermic animals. There was no significant difference between the normothermic and hypothermic animals for arginine, taurine, alanine, glutamine, histadine, glycine, threonine, tyrosine, and asparagine. No significant effect of hypothermia on lactate or lactate/pyruvate was noted. However, the mean level of lactate tended to be lower and recovery was quicker in hypothermic animals. The results of the present study suggest that moderate hypothermia does not attenuate extracellular accumulation of EAAs or markedly improve energy metabolism in our model. Instead, our findings raise the possibility that moderate hypothermia prolongs the duration of glutamate receptor overactivation. Since hypothermia effectively attenuates glutamate release in CNS and spinal cord ischemia models our results suggest different mechanisms of extracellular accumulation of EAAs in ischemia and trauma.
我们在大鼠身上评估了中度低温（30 - 31摄氏度）对严重脊髓压迫后氨基酸细胞外水平的影响，特别关注兴奋性氨基酸（EAA）谷氨酸和天冬氨酸、乳酸和丙酮酸。进行了T7和T8椎板切除术。将探针插入背角，并在施加5分钟严重压迫之前1.5小时和之后4小时进行微透析。每隔10分钟收集透析液样本，并通过高效液相色谱法进行分析。在体温正常（37.5摄氏度）的动物中，谷氨酸水平在创伤后的最初10分钟内呈数倍升高并达到峰值。低温动物在创伤后也出现了类似的升高，在损伤后20分钟内具有统计学意义。与体温正常的动物相比，低温动物在损伤后20至70分钟时谷氨酸水平显著更高。天冬氨酸在损伤后也显著增加。两组的峰值浓度相似，而低温动物的恢复延迟。在精氨酸、牛磺酸、丙氨酸、谷氨酰胺、组氨酸、甘氨酸、苏氨酸、酪氨酸和天冬酰胺方面，体温正常和低温的动物之间没有显著差异。未观察到低温对乳酸或乳酸/丙酮酸有显著影响。然而低温动物的乳酸平均水平倾向于更低且恢复更快。本研究结果表明，在我们的模型中，中度低温不会减弱EAA的细胞外积累或显著改善能量代谢。相反，我们的研究结果提出了中度低温会延长谷氨酸受体过度激活持续时间的可能性。由于低温在中枢神经系统和脊髓缺血模型中能有效减弱谷氨酸释放，我们的结果表明在缺血和创伤中EAA细胞外积累的机制不同。
