Katayama Y, Becker D P, Tamura T, Hovda D A
Division of Neurosurgery, University of California School of Medicine, Los Angeles.
J Neurosurg. 1990 Dec;73(6):889-900. doi: 10.3171/jns.1990.73.6.0889.
An increase in extracellular K+ concentration ([K+]c) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]c increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]c, the extracellular concentration of glutamate ([Glu]c) was measured along with [K+]c. The results indicate that a relatively specific increase in [Glu]c (as compared with other amino acids) was induced concomitantly with the increase in [K+]c. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]c. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury.
通过微透析法证实，流体冲击性脑损伤后大鼠海马细胞外钾离子浓度（[K+]c）升高。采用原位给予0.1 mM河豚毒素（一种有效的神经元放电抑制剂）和0.5至20 mM钴（一种Ca++通道阻滞剂）来研究神经元放电的作用。轻度损伤后观察到[K+]c有小幅短暂升高（1.40至2.15倍），但随着损伤严重程度超过一定阈值（昏迷200至250秒），在无明显形态学损伤的情况下会诱导出更明显、持续时间更长的升高（4.28至5.90倍）。预先给予河豚毒素可减少小幅短暂升高，但钴无此作用，表明神经元放电是这种升高的来源。相反，较大且持续时间更长的升高对河豚毒素有抗性且部分依赖Ca++，提示涉及神经递质释放。为了检验兴奋性氨基酸神经递质谷氨酸的释放介导[K+]c升高这一假说，同时测量了谷氨酸的细胞外浓度（[Glu]c）与[K+]c。结果表明，[Glu]c相对特异性升高（与其他氨基酸相比）与[K+]c升高同时出现。此外，原位给予1至25 mM犬尿氨酸（一种兴奋性氨基酸拮抗剂）可有效减弱[K+]c的升高。剂量反应曲线表明，犬尿氨酸在基本阻断所有兴奋性氨基酸受体亚型的浓度下可获得最大效应。这些数据表明，冲击性脑损伤会导致大量钾离子通量，这可能与脑损伤后立即发生的兴奋性氨基酸的无差别释放有关。
