Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Universitario de Santiago, University of Santiago de Compostela, IDIS, Santiago de Compostela, Spain.
PLoS One. 2012;7(8):e44191. doi: 10.1371/journal.pone.0044191. Epub 2012 Aug 28.
Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.
谷氨酸兴奋性毒性、代谢率和炎症反应与中风急性期体温的有害影响有关。到目前为止，温度与这些机制的关系已经分别进行了研究。然而，为了阐明它们对温度介导的缺血性损伤的贡献，有必要同时研究温度对这些机制的影响。我们使用非侵入性磁共振波谱在缺血动物模型中同时测量大脑中的温度、谷氨酸兴奋性毒性和代谢率。通过外周血中的分子血清标志物测量对缺血的免疫反应。我们将动物分组置于不同的实验条件下（33°C 的低温、37°C 的正常体温和 39°C 的高温），并通过全身注射谷氨酸和草酰乙酸来调节大脑中的谷氨酸水平，将这些条件结合起来。我们发现，通过调节谷氨酸水平可以中和高温的有害影响和低温的有益影响，然而，对炎症反应和代谢率的分析表明，它们对缺血性损伤的影响不如谷氨酸兴奋性毒性重要。我们的结论是，谷氨酸兴奋性毒性是脑中风急性期体温影响的关键分子机制。
