Seizures induced by homocysteic acid in immature rats are prevented by group III metabotropic glutamate receptor agonist (R,S)-4-phosphonophenylglycine
Seizures induced by homocysteic acid in immature rats are prevented by group III metabotropic glutamate receptor agonist (R,S)-4-phosphonophenylglycine
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DOI：
10.1016/s0014-4886(02)00047-x
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发表时间：
2003-03-01
影响因子：
5.3
通讯作者：
Mares, P
中科院分区：
文献类型：
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作者：
Folbergrová, J;Haugvicová, R;Mares, P
本研究观察了代谢型谷氨酸受体（mGluR）激动剂（R，S）-4-膦酰基苯甘氨酸（（R，S）-PPG）对侧脑室注射DL-同型半胱氨酸（DL-HCA，600 nmol/侧）诱发的幼鼠惊厥的潜在抗惊厥作用。在全身性阵挛性强直性发作期间处死大鼠幼崽，类似于输注后45至50分钟。使用可比的时间间隔处死接受（R，S）-PPG的幼仔。低剂量（R，S）-PPG（10 nmol，icv）提供了显著的抗惊厥作用，该作用可通过选择性III组mGluR拮抗剂（R，S）-α-甲基丝氨酸-O-磷酸盐预处理消除。全身阵挛性强直性癫痫发作被完全抑制，通常伴随这些癫痫发作的皮质能量代谢物变化要么正常化（葡萄糖和糖原减少），要么显着改善（乳酸盐积累）。尽管没有明显的运动现象，脑电图记录显示零星的发作活动，主要是在背海马。这种活动扩散到额叶皮层是相当罕见的。预处理组大鼠发作期脑电潜伏期明显延长。我们的数据表明，（R，S）-PPG的主要作用可能与癫痫发作扩散有关。（R，S）-PPG单独给药不会引起任何明显的行为副作用;它不会改变EEG模式，也不会影响皮质代谢物水平，但葡萄糖浓度升高除外。目前的研究结果表明，第三组mGlu受体激动剂可能是治疗儿童癫痫的治疗意义。(C)2003 Elsevier Science（美国）。All rights reserved.
The potential anticonvulsant effect of group III metabotropic glutamate receptor (mGluR) agonist (R,S)-4-phosphonophenylglycine ((R,S)-PPG) against seizures induced in immature 12-day-old rats by bilateral intracerebroventricular (icv) infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side) was examined in the present study. Rat pups were sacrificed during generalized clonic-tonic seizures, similar to45 to 50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received (R,S)-PPG. Low doses of (R,S)-PPG (10 nmol, icv) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group III mGluR antagonist (R,S)-alpha-methylserine-O-phosphate. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (glucose and glycogen decreases) or markedly ameliorated (an accumulation of lactate). Despite the absence of obvious motor phenomena, EEG recordings revealed sporadic ictal activity, mostly in the dorsal hippocampus. Spreading of this activity into the frontal cortex was rather exceptional. The latency of ictal EEG in pretreated rats was significantly prolonged. Our data suggest that the predominant effect of (R,S)-PPG might concern seizure spread. The administration of (R,S)-PPG alone did not cause any overt behavioral side effects; it did not change the EEG pattern and did not influence cortical metabolite levels, with the exception of increased concentrations of glucose. The present findings suggest that group III mGlu receptor agonists may be of therapeutic significance for treating childhood epilepsies. (C) 2003 Elsevier Science (USA). All rights reserved.