Folbergrová J, Haugvicová R, Mares P
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, 142 20, Czech Republic.
Exp Neurol. 2000 Jan;161(1):336-45. doi: 10.1006/exnr.1999.7264.
Bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA) (600 nmol on each side) to immature 12-day-old rats induced generalized clonic-tonic seizures, recurring frequently for at least 90 min, with a high rate of survival. Electrographic recordings from sensorimotor cortex, hippocampus, and striatum demonstrated isolated spikes in the hippocampus and/or striatum as the first sign of dl-HCA action. Generalization of epileptic activity occurred during generalized clonic-tonic seizures, but electroclinical correlation was very low; dissociation between EEG pattern and motor phenomena was common. Seizures were accompanied by large decreases of cortical glucose and glycogen and by approximately 7- to 10-fold accumulation of lactate. ATP and phosphocreatine (PCr) levels remained unchanged even during longlasting (3 h) convulsions. Metabolite levels became normalized during the recovery period (24 h). The examination of the effect of selected antagonists of NMDA [AP7 (18.5 and 37 mg/kg, respectively), MK-801 (0.5 mg/kg)] and non-NMDA [NBQX (10, 15 and 30 mg/kg, respectively)] receptors revealed that seizures could be attenuated or prevented (depending on the dose employed) by antagonists of both NMDA and non-NMDA receptors, as evaluated not only according to the suppression of behavioral manifestations of seizures, but also in terms of the protection of metabolite changes accompanying seizures. All antagonists employed, when given alone in the same doses as those used for seizure protection, did not influence metabolite levels, with the exception of increased glucose concentrations. Furthermore, the pronounced anticonvulsant effect could be achieved by the combined treatment with low subthreshold doses of NMDA (AP7) and non-NMDA (NBQX) receptor antagonists, which may be of potential significance for a new approach to the treatment of epilepsy.
向12日龄未成熟大鼠双侧脑室内注入dl-高半胱氨酸（DL-HCA）（每侧600 nmol）可诱发全身性阵挛-强直性惊厥，频繁发作至少90分钟，存活率高。感觉运动皮层、海马体和纹状体的脑电图记录显示，海马体和/或纹状体出现孤立的尖峰是dl-HCA作用的首个迹象。癫痫活动在全身性阵挛-强直性惊厥期间发生泛化，但电临床相关性非常低；脑电图模式与运动现象之间的分离很常见。惊厥伴有皮层葡萄糖和糖原大幅减少，乳酸积累约7至10倍。即使在长时间（3小时）惊厥期间，三磷酸腺苷（ATP）和磷酸肌酸（PCr）水平仍保持不变。恢复期（24小时）代谢物水平恢复正常。对N-甲基-D-天冬氨酸（NMDA）[分别为AP7（18.5和37 mg/kg）、MK-801（0.5 mg/kg）]和非NMDA[分别为NBQX（10、15和30 mg/kg）]受体的选定拮抗剂的作用研究表明，NMDA和非NMDA受体的拮抗剂均可减轻或预防惊厥（取决于所用剂量），这不仅根据惊厥行为表现的抑制情况来评估，还根据对惊厥伴随的代谢物变化的保护情况来评估。所有单独使用的拮抗剂，当给予与惊厥保护所用相同剂量时，除葡萄糖浓度升高外，均不影响代谢物水平。此外，联合使用低亚阈值剂量的NMDA（AP7）和非NMDA（NBQX）受体拮抗剂可产生显著的抗惊厥作用，这可能对癫痫治疗的新方法具有潜在意义。
