Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy
Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy
复制标题
DOI：
10.1016/s0920-1211(01)00299-6
复制
发表时间：
2001-11-01
影响因子：
2.2
通讯作者：
Nehlig, A
中科院分区：
文献类型：
--
作者：
André, V;Ferrandon, A;Nehlig, A
在颞叶癫痫(TLE)中，参与致痫回路发展的结构的性质仍不清楚。在锂-匹罗卡品模型中，神经元损伤既发生在癫痫起始和维持回路(前脑边缘系统)的结构中，也发生在传播区(皮质和丘脑)和癫痫远程控制回路(黑质网状部)中。为了确定脑区保护是否能预防癫痫持续状态(SE)所致癫痫的发生，以及确定与TLE发生有关的脑结构，我们研究了长期暴露于Vigabatrin(GVG)对锂-匹罗卡品SE所致神经元损伤和癫痫发生的影响。动物于注射匹罗卡品后10min开始给予SE和GVG(250 mg/kg)，每日1次，持续45d。将这些Pilo-GVG大鼠与SE+每日生理盐水治疗(Pilo-生理盐水)的大鼠以及未接受SE的对照组(生理盐水)进行比较。GVG处理后可引起明显的损伤。CA3几乎完全神经保护。治疗对CA1有有效的保护作用，对齿状回的门部有中等的保护作用，而内嗅皮层的损害则略有加重。所有Pilo-GVG和Pilo-生理盐水大鼠在相同的潜伏期后均出现癫痫。与生理盐水组相比，Pilo-GVG组大鼠海马区谷氨酸脱羧酶(GAD67)免疫反应恢复，但上丘光层和黑质网状部GAD67免疫反应增强。因此，目前的数据表明，对海马伞状角主细胞的神经保护不足以防止癫痫的发生，提示本研究中未受保护的海马门和海马外结构可能在该模型自发性反复发作的发生中发挥作用。更远-更多。这项在非癫痫大鼠身上进行的研究表明，长期使用GABAmic药物治疗会上调GAD67蛋白在大脑特定区域的表达。不受癫痫发作的影响。(C)2001 Elsevier Science B.V.保留所有权利。
In temporal lobe epilepsy (TLE), the nature of the structures involved in the development of the epileptogenic circuit is still not clearly identified. In the lithium-pilocarpine model, neuronal damage occurs both in the structures belonging to the circuit of initiation and maintenance of the seizures (forebrain limbic system) as well as in the propagation areas (cortex and thalamus) and in the circuit of remote control of seizures (substantia nigra pars reticulata). In order to determine whether protection of some brain areas could prevent the epileptogenesis induced by status epilepticus (SE) and to identify the cerebral structures involved in the genesis of TLE, we studied the effects of the chronic exposure to Vigabatrin (gamma-vinyl-GABA, GVG) on neuronal damage and epileptogenesis induced by lithium-pilocarpine SE. The animals were subjected to SE and GVG treatment (250 mg/kg) was initiated at 10 min after pilocarpine injection and maintained daily for 45 days. These pilo-GVG rats were compared with rats subjected to SE followed by a daily saline treatment (pilo-saline) and to control rats not subjected to SE (saline-saline). GVG treatment induced a marked. almost total neuroprotection in CA3. an efficient protection in CA1 and a moderate one in the hilus of the dentate gyrus while damage in the entorhinal cortex was slightly worsened by the treatment. All pilo-GVG and pilo-saline rats became epileptic after the same latency. Glutamic acid decarboxylase (GAD67) immunoreactivity was restored in pilo-GVG rats compared with pilo-saline rats in all areas of the hippocampus, while it was increased over control levels in the optical layer of the superior colliculus and the substantia nigra pars reticulata. Thus, the present data indicate that neuroprotection of principal cells in the Ammon's horn of the hippocampus is not sufficient to prevent epileptogenesis, suggesting that the hilus and extra-hippocampal structures, that were not protected in this study, may play a role in the genesis of spontaneous recurrent seizures in this model. Further-more. the study performed in non-epileptic rats indicates that chronic treatment with a GABAmimetic drug upregulates the expression of the protein GAD67 in specific areas of the brain. independently from the seizures. (C) 2001 Elsevier Science B.V. All rights reserved.