Hillered L, Hallström A, Segersvärd S, Persson L, Ungerstedt U
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
J Cereb Blood Flow Metab. 1989 Oct;9(5):607-16. doi: 10.1038/jcbfm.1989.87.
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 cerebral 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.
本研究的目的是，采用脑内微透析作为采样技术，测量局灶性脑缺血大鼠纹状体中细胞外液（ECF）中乳酸、丙酮酸、嘌呤、氨基酸、多巴胺及多巴胺代谢产物的浓度变化。实验前2小时，将微透析探针双侧插入尾状核-壳核外侧部。通过永久性左侧大脑中动脉闭塞（MCAO）诱导缺血。微透析样本采用高效液相色谱法进行分析。MCAO后，闭塞侧ECF中乳酸、腺苷、肌苷和次黄嘌呤的浓度显著升高，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-氨基丁酸和多巴胺水平的显著升高。丙氨酸/酪氨酸也显著增加，而其他氨基酸变化较小或无变化。同时，多巴胺代谢产物3,4-二羟基苯乙酸和高香草酸的ECF水平降低。右侧未闭塞侧所测的任何代谢产物均无显著增加。关于脑缺血中的兴奋性毒性概念，得出的结论是，在局灶性脑缺血急性期，ECF中充斥着潜在有害（如天冬氨酸、谷氨酸和多巴胺）和保护性（如牛磺酸、GABA和腺苷）物质。这些事件对缺血半暗带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中测得的乳酸、肌苷和次黄嘌呤，可能在缺血性脑的神经代谢监测中具有诊断和/或预后价值。
