Nilsson P, Hillered L, Pontén U, Ungerstedt U
Department of Neurosurgery, University Hospital, Uppsala, Sweden.
J Cereb Blood Flow Metab. 1990 Sep;10(5):631-7. doi: 10.1038/jcbfm.1990.115.
The aim of this study was to measure extracellular chemical changes in the cerebral cortex in response to compression contusion trauma in rats. Energy-related metabolites (i.e., lactate, pyruvate, adenosine, inosine, and hypoxanthine) and amino acids were harvested from the extracellular fluid (ECF) using microdialysis and analyzed by high-performance liquid chromatography. The measurements were performed in cortical tissue, where neuronal injury occurs in this model. The severity of the trauma was varied by using different depths of impact: mild trauma, 1.5 mm; severe trauma, 2.5 mm. The trauma induced a dramatic increase in the ECF levels of energy-related metabolites that was conditioned by the severity of the insult. The ECF level of taurine, glutamate, aspartate, and gamma-aminobutyric acid (GABA) also rose markedly, while other amino acids did not change significantly. The results suggest that the trauma induced a transient, profound focal disturbance of energy metabolism in the cortical tissue, probably as a result of mechanically induced disruption of ion homeostasis and reduced blood flow in combination. The data support the potential role of glutamate and aspartate as mediators of traumatic brain injury. However, the concomitantly released adenosine, GABA, and taurine may be protective and ameliorate excitotoxicity. In analogy with the reported cumulative damaging effects of repeated ischemic insults, the observed ECF changes may help explain the vulnerability of traumatized brain tissue to secondary ischemia.
本研究的目的是测量大鼠大脑皮质在受到压迫性挫伤创伤时细胞外的化学变化。使用微透析从细胞外液（ECF）中采集能量相关代谢物（即乳酸、丙酮酸、腺苷、肌苷和次黄嘌呤）和氨基酸，并通过高效液相色谱法进行分析。测量在皮质组织中进行，该模型中神经元损伤就发生在此处。通过使用不同的撞击深度来改变创伤的严重程度：轻度创伤，1.5毫米；重度创伤，2.5毫米。创伤导致能量相关代谢物的细胞外液水平急剧升高，这取决于损伤的严重程度。牛磺酸、谷氨酸、天冬氨酸和γ-氨基丁酸（GABA）的细胞外液水平也显著升高，而其他氨基酸则没有明显变化。结果表明，创伤导致皮质组织中能量代谢出现短暂而严重的局灶性紊乱，这可能是机械性诱导的离子稳态破坏和血流减少共同作用的结果。数据支持谷氨酸和天冬氨酸作为创伤性脑损伤介质的潜在作用。然而，同时释放的腺苷、GABA和牛磺酸可能具有保护作用并减轻兴奋性毒性。与报道的反复缺血性损伤的累积损伤效应类似，观察到的细胞外液变化可能有助于解释创伤性脑组织对继发性缺血的易损性。
