The role of excitatory amino acids in traumatic brain injury and effects of hypothermia

目的：探讨低温对脑挫伤后兴奋性氨基酸(EaaS)释放和脑血流量(CBF)的影响。研究低温对缺氧引起的氨基酸变化的影响。方法：选用成年雄性Wistar大鼠。动物分为常温组(37ﾟC)和亚低温组(32ﾟC)。采用减重的方法在顶叶皮质制造脑挫伤模型。(1)用氢清除法监测脑血流量，用脑内微透析法测定脑皮质EaS水平。(2)脑缺氧(PaO_2：30~40 mm Hg)60min。用激光多普勒血流仪测定脑血流量，用微透析法测定细胞外EaAs浓度。(3)脑挫伤后出现缺氧。结果：(1)两组…患者的脑血流量及脑脊液中总氨基酸浓度均高于正常对照组更多的组在挫伤后显着减少，但从未低于缺血阈值。各组大鼠脑挫伤后皮质EaAs水平均明显升高。然而，这些增加在低温下比常温下的大鼠更大。(2)两组动脉压在低氧时均明显回升，停止低氧后恢复正常。两组的脑血流量在低氧期间都有轻微的增加。亚低温消除了常温条件下出现的EAA激增。(3)各组挫伤后EAA水平均显著升高，且低温组较常温组升高更明显(1)。常温动物的EAA水平在低氧诱导后再次升高。结论：亚低温对创伤性脑损伤的脑保护作用可能不是通过间质兴奋性氨基酸的减少，而是通过其他机制实现的。推测当脑血流量维持在缺血阈值以上时，低温的突触后效应可能比突触前效应更重要。脑缺氧是颅脑损伤复杂的病理机制之一。这些研究结果提示，低温可改善脑缺氧引起的继发性损害。较少

Purpose : The purpose of this study was to investigate the effects of hypothermia on the release of the excitatory amino acids (EAAs) and cerebral blood flow (CBF) during cerebral contusion. The effects of hypothermia on hypoxia-induced changes in the amino acids were also investigated.Methods : Adult male Wistar rats were used. The animals were devieded two experimental groups : normothermia group (37ﾟC) and hypothermia group (32ﾟC). Cerebral contusion was created in the parietal cortex by a weight-drop method. (1) CBF was monitored using the hydrogen clearance technique, and cortical levels of EAAs were measured by intracerebral microdialysis. (2) Cerebral hypoxia (PaO2 : 30-40 mmHg) was induced for 60 min. CBF was measured by laser-Doppler flowmetry, and the extracelular concentrations of EAAs were measured by microdialysis. (3) After cerebral contusion was created, hypoxia was induced. CBF and the EAA concentrations were measured by the same methods as (2).Results : (1) CBF in both … More groups decreased significantly after contusion but never fell below the threshold for ischemia. Cortical levels of EAAs were significantly increased after contusion in each group. However, these increases were greater in the hypothermic than in the normothermic rats. (2) Arterial blood pressurefell markedly during hypoxia in both groups, and returned to the normal range after cessation of hypoxia. CBF showed modest increases during hypoxia in both groups. Mild hypothermia abolished the EAA surge seen under norjmothermic conditions. (3) EAA levels were significantly increased after contusion in each group, and these increases were greater in the hypothermic than in the normothermic rats as the experiment (1). The EAA levels of the normothermic animals increased again after hypoxia induction. Mild hypothermia abolished such hypoxia-induced EAA surge.Conclusion : Hypothermic cerebroprotection in traumatic brain injury (TBI) is likely to occur through a kmechanism other than reduction in interstitial excitatory amino acids. It is postulated that the postsynaptic effects of hypothermia may be more important than the presynaptic effects, when CBF is kept above the ischemic threshold. Cerebral hypoxia contributes to the complex spectrum of pathology of TBI.The results of these study suggest that secondary damage caused by cerebral hypoxia can be ameliorated by hypothermia. Less