During M J, Fried I, Leone P, Katz A, Spencer D D
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510.
J Neurochem. 1994 Jun;62(6):2356-61. doi: 10.1046/j.1471-4159.1994.62062356.x.
The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory complex partial epilepsy underwent stereotactic implantation of combination depth electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous complex partial seizures with secondary generalization, extracellular lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactate content was restricted to the side of seizure activity. Between seizures, extracellular lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical seizures increase nonoxidative glucose metabolism significantly as measured by the generation of extracellular lactate. Furthermore, the increase in extracellular lactate levels is limited to the site of seizure activity. Lactate is transported extracellularly via a lactate/proton cotransporter, therefore, the rise in extracellular lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.
采用乳酸造影法（即使用微透析技术在体在线测量乳酸水平）研究了临床自发性发作的癫痫对细胞外液乳酸的影响。对实验动物的研究表明，通过微透析测量的细胞外乳酸生成是局部葡萄糖利用的一个指标，并且在生理条件下依赖于神经元的活动。药物难治性复杂部分性癫痫患者接受立体定向手术，将深度电极/微透析探头组合植入双侧海马体7 - 16天。在伴有继发性泛化的自发性复杂部分性发作期间，细胞外乳酸水平升高了91±32%。此外，这种升高持续了60 - 90分钟。在未传播至对侧海马体的单侧海马体发作期间，乳酸含量的增加仅限于发作活动的一侧。在发作间期，细胞外乳酸水平与发作间期棘波的频率相关。总之，这些数据表明，短暂的临床发作会显著增加通过细胞外乳酸生成所测量的非氧化葡萄糖代谢。此外，细胞外乳酸水平的升高仅限于发作活动的部位。乳酸通过乳酸/质子协同转运体转运至细胞外，因此，细胞外乳酸水平的升高可能介导了与发作活动相关的pH0下降。由于细胞外区室的酸化对神经元兴奋性有抑制作用，细胞外乳酸含量的升高可能是发作停止和发作后不应期的一种机制。此外，细胞外乳酸也可能介导与频繁发作间期棘波相关的癫痫易感性降低。
