CIRCUIT MECHANISMS OF SEIZURES IN THE PILOCARPINE MODEL OF CHRONIC EPILEPSY - CELL LOSS AND MOSSY FIBER SPROUTING
CIRCUIT MECHANISMS OF SEIZURES IN THE PILOCARPINE MODEL OF CHRONIC EPILEPSY - CELL LOSS AND MOSSY FIBER SPROUTING
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DOI：
10.1111/j.1528-1157.1993.tb02123.x
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发表时间：
1993-11-01
期刊：
影响因子：
5.6
通讯作者：
FINCH, DM
中科院分区：
文献类型：
--
作者：
MELLO, LEAM;CAVALHEIRO, EA;FINCH, DM
我们使用慢性自发性复发性癫痫发作的毛果芸香碱模型来评估颗粒上齿状出芽的时间过程，并评估癫痫组织中发生的几种变化与颞叶癫痫实验模型的不同行为表现之间的关系。毛果芸香碱诱导的癫痫持续状态 (SE) 总是会导致齿状回 (DG) 门细胞丢失并导致自发性复发性癫痫发作。 DG 和海马亚区 CA1 和 CA3 中也经常注意到细胞损失。癫痫发作平均在 SE 诱导后 15 天（静默期）开始出现，每只动物以不同的频率复发，并持续到动物存活为止（325 天）。癫痫动物体内DG的颗粒细胞层分散，neo-Timm染色显示颗粒上和颗粒内杂乱的纤维出芽。颗粒上杂乱纤维出芽和齿状颗粒细胞分散在 SE 后早期就开始出现（分别早在 4 天和 9 天），并在 100 天时达到稳定水平。海马区 CA3 细胞丢失程度较高的动物显示慢性癫痫发作较晚（r = 0.83，p < 0.0005），表明 CA3 代表癫痫发作传播的途径之一。这些结果表明，慢性癫痫发作的毛果芸香碱模型复制了人类颞叶癫痫的几个特征（海马细胞丢失、颗粒上和颗粒内杂乱纤维出芽、齿状颗粒细胞分散、自发性复发性癫痫发作），并且它可能是研究这种人类疾病的有用模型。研究结果还表明，尽管特定区域一定量的细胞丢失可能是慢性癫痫发作的必要条件，但过多的细胞丢失可能会阻碍癫痫的发生。
We used the pilocarpine model of chronic spontaneous recurrent seizures to evaluate the time course of supragranular dentate sprouting and to assess the relation between several changes that occur in epileptic tissue with different behavioral manifestations of this experimental model of temporal lobe epilepsy. Pilocarpine-induced status epilepticus (SE) invariably led to cell loss in the hilus of the dentate gyrus (DG) and to spontaneous recurrent seizures. Cell loss was often also noted in the DG and in hippocampal subfields CA1 and CA3. The seizures began to appear at a mean of 15 days after SE induction (silent period), recurred at variable frequencies for each animal, and lasted for as long as the animals were allowed to survive (325 days). The granule cell layer of the DG was dispersed in epileptic animals, and neo-Timm stains showed supra- and intragranular messy fiber sprouting. Supragranular messy fiber sprouting and dentate granule cell dispersion began to appear early after SE (as early as 4 and 9 days, respectively) and reached a plateau by 100 days. Animals with a greater degree of cell loss in hippocampal field CA3 showed later onset of chronic epilepsy (r = 0.83, p < 0.0005), suggesting that CA3 represents one of the routes for seizure spread. These results demonstrate that the pilocarpine model of chronic seizures replicates several of the features of human temporal lobe epilepsy (hippocampal cell loss, supra- and intragranular messy fiber sprouting, dentate granule cell dispersion, spontaneous recurrent seizures) and that it may be a useful model for studying this human condition. The results also suggest that even though a certain amount of cell loss in specific areas may be essential for chronic seizures to occur, excessive cell loss may hinder epileptogenesis.