DYNAMICS OF EXTRACELLULAR METABOLITES IN THE STRIATUM AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN THE RAT MONITORED BY INTRACEREBRAL MICRODIALYSIS
DYNAMICS OF EXTRACELLULAR METABOLITES IN THE STRIATUM AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN THE RAT MONITORED BY INTRACEREBRAL MICRODIALYSIS
复制标题
DOI：
10.1038/jcbfm.1989.87
复制
发表时间：
1989-10-01
影响因子：
6.3
通讯作者：
UNGERSTEDT, U
中科院分区：
文献类型：
--
作者：
HILLERED, L;HALLSTROM, A;UNGERSTEDT, U
本研究采用脑内微透析作为采样技术，测量局灶性中央缺血大鼠纹状体中乳酸、丙酮酸、嘌呤、氨基酸、多巴胺和多巴胺代谢物的细胞外液（ECF）浓度的变化。实验前2小时将微透析探针插入双侧尾壳核外侧。永久性大脑中动脉闭塞（MCAO）诱导左脑缺血。采用高效液相色谱法对微透析样品进行分析。MCAO后，闭塞侧ECF中乳酸、腺苷、肌苷、次黄嘌呤浓度明显升高，而丙酮酸无明显变化。这些变化伴随着天冬氨酸、谷氨酸、牛磺酸、γ的显著升高。-氨基丁酸和多巴胺丙氨酸、酪氨酸也显著增加，而其他氨基酸变化不大或没有变化。同时，多巴胺代谢物3,4-二羟基苯乙酸酯和高香草酸的ECF水平下降。在右侧未闭塞侧测量的任何代谢物均无显著增加。关于脑缺血兴奋性毒性的概念，我们得出结论，在局灶性脑缺血的急性阶段，ECF充满潜在有害（如天冬氨酸、谷氨酸和DA）和保护性（如牛磺酸、GABA和腺苷）的药物。这些事件对缺血半暗区细胞死亡发展的相对重要性有待阐明。此外，通过脑内微透析在ECF中测量乳酸、肌苷和次黄嘌呤，可能证明在缺血性脑的神经代谢监测中具有诊断和/或预后价值。
The aim of this study was to measure changes in the extracellular fluid (ECF) concentration of lactate, pyruvate, purines, amino acids, dopamine, and dopamine metabolites in the striatum of rats subjected to focal ceretral ischemia, using intracerebral microdialysis as the sampling technique. Microdialysis probes were inserted into the lateral part of the caudate-putamen bilaterally 2 h before the experiment. Ischemia was induced by permanent middle cerebral artery occlusion (MCAO) on the left side. Microdialysis samples were analyzed by high performance liquid chromatography. Following MCAO, the concentration of lactate, adenosine, inosine, and hypoxanthine rose markedly in the ECF on the occluded side, while there was no significant change in pyruvate. These changes were accompanied by dramatically elevated levels of aspartate, glutamate, taurine, .gamma.-aminobutyric acid, and dopamine. There was also a marked increase in alanine, tyrosine, while minor or no changes occurred with other amino acids. Concomitantly, the ECF level of the dopamine metabolites 3,4-dihydroxyphenylacetate and homovanillic acid decreased. There was no significant increase in any of the metabolites measured on the right, nonoccluded side. In relation to the concept of excitotoxicity in brain ischemia, it is concluded that during the acute stage of focal cerebral ischemia, the ECF is flooded with both potentially harmful (e.g., aspartate, glutamate, and DA) and protective (e.g. taurine, GABA, and adenosine) agents. The relative importance of these events for the development of cell death in the ischemic penumbra needs to be elucidated. In addition, lactate, inosine, and hypoxanthine, measured in the ECF by intracerebral microdialysis, may prove to have diagnostic and/or prognostic value in neurometabolic monitoring of the ischemic brain.