Pan J C, Pei Y Q, An L, Lai L, D'Hooge R, De Deyn P P
Department of Pharmacology, Beijing Medical University, School of Basic Medical Sciences, People's Republic of China.
Neurosci Lett. 1996 May 10;209(2):121-4. doi: 10.1016/0304-3940(96)12615-x.
Guanidinosuccinic acid (GSA) is a guanidino compound found in mammalian central nervous system and physiological fluids. Its level has been found to be greatly increased in serum and cerebrospinal fluid of patients with renal failure, and the compound is suggested to play a role in uremic encephalopathy. In this report we examined the behavioral, electrographic and morphological effects of intrahippocampal GSA injection in unanesthetized rats. Intrahippocampal administration of 2 microliters GSA solution (3.5 nM) was followed by behavior observation, and electrohippocampographic and electrocorticographic recording. GSA-injected animals showed partial clonic seizures leading to generalized clonic seizures, and eventually status epilepticus. These were accompanied by epileptiform electrographic discharges. During generalized clonic seizures, the electrohippocampogram showed arythmic bursting spikes. Epileptiform electric activity persisted even after the generalized clonic convulsions had stopped, and lasted until the animals were killed, 5 days following injection. Microscopic examination of brain slices of these rats revealed severe neural damage in CA1 area of hippocampus. Treatment of rats with the non-competitive NMDA receptor antagonist ketamine prevented both partial and generalized clonic seizures, epileptiform electrographic discharges, and GSA-induced hippocampal damage.
胍基琥珀酸（GSA）是一种在哺乳动物中枢神经系统和生理液中发现的胍基化合物。已发现肾衰竭患者血清和脑脊液中其水平大幅升高，并且该化合物被认为在尿毒症性脑病中起作用。在本报告中，我们研究了在未麻醉大鼠海马内注射GSA的行为、脑电图和形态学效应。海马内注射2微升GSA溶液（3.5纳摩尔）后进行行为观察以及海马电图和皮质电图记录。注射GSA的动物出现部分阵挛性惊厥，进而发展为全身性阵挛性惊厥，最终演变为癫痫持续状态。这些惊厥伴有癫痫样脑电图放电。在全身性阵挛性惊厥期间，海马电图显示无节律的爆发性尖峰。即使在全身性阵挛性惊厥停止后，癫痫样电活动仍持续存在，并一直持续到注射后5天处死动物时。对这些大鼠脑切片的显微镜检查显示海马CA1区有严重的神经损伤。用非竞争性NMDA受体拮抗剂氯胺酮治疗大鼠可预防部分和全身性阵挛性惊厥、癫痫样脑电图放电以及GSA诱导的海马损伤。
