Soukupova M, Binaschi A, Falcicchia C, Palma E, Roncon P, Zucchini S, Simonato M
Department of Medical Sciences, Section of Pharmacology, Neuroscience Center, University of Ferrara and National Institute of Neuroscience, Via Fossato di Mortara 17-19, Ferrara, Italy.
Department of Physiology and Pharmacology, University of Roma "Sapienza", Piazzale Aldo Moro 5, Roma, Italy; IRCCS San Raffaele, Via della Pisana 235, Roma, Italy.
Neuroscience. 2015 Aug 20;301:246-53. doi: 10.1016/j.neuroscience.2015.06.013. Epub 2015 Jun 11.
An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.
在癫痫发作期间，无论是人类还是动物，海马体中兴奋性氨基酸的释放都会持续增加。然而，关于癫痫发生过程中以及已确诊癫痫的发作间期慢性期谷氨酸和天冬氨酸的细胞外水平，人们了解得很少，甚至一无所知。本研究的目的是使用体内微透析技术，系统评估在实验性颞叶癫痫自然病程的不同时间点，基础状态和高钾诱发条件下癫痫发作活动与海马体谷氨酸和天冬氨酸细胞外水平变化之间的关系。评估了海马体的细胞外谷氨酸和天冬氨酸水平：匹鲁卡品诱导的癫痫持续状态（SE）后24小时；自发癫痫发作前的潜伏期；首次自发癫痫发作后立即进行评估；在慢性（癫痫）期进行评估。我们发现：（i）在慢性期的发作间期，基础（自发）谷氨酸流出增加，而基础天冬氨酸流出在疾病的整个过程中保持稳定；（ii）高钾灌注增加了对照组和匹鲁卡品处理组动物的谷氨酸和天冬氨酸流出，并且慢性组中谷氨酸的溢出明显增加。我们的数据表明，癫痫大鼠海马体中的谷氨酸能信号传导得以保留甚至增强，因此可能有利于自发复发性癫痫发作的发生。与γ-氨基丁酸信号传导受损（Soukupova等人，2014年）一起，这些数据表明在慢性癫痫状态下，兴奋/抑制平衡向兴奋方向转变。
