Mello L E, Cavalheiro E A, Tan A M, Kupfer W R, Pretorius J K, Babb T L, Finch D M
Department of Neurology, University of California, Los Angeles.
Epilepsia. 1993 Nov-Dec;34(6):985-95. doi: 10.1111/j.1528-1157.1993.tb02123.x.
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 mossy fiber sprouting. Supragranular mossy 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 mossy 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.
我们使用毛果芸香碱诱导的慢性自发性复发性癫痫模型来评估颗粒上层齿状回发芽的时间进程，并评估癫痫组织中发生的几种变化与该颞叶癫痫实验模型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）总是导致齿状回（DG）门区细胞丢失和自发性复发性癫痫发作。在DG以及海马亚区CA1和CA3中也经常观察到细胞丢失。癫痫发作在SE诱导后平均15天开始出现（潜伏期），每只动物的发作频率各不相同，并且只要动物存活（325天）就会持续发作。DG的颗粒细胞层在癫痫动物中分散，新的Timm染色显示颗粒上层和颗粒内苔藓纤维发芽。颗粒上层苔藓纤维发芽和齿状颗粒细胞分散在SE后早期开始出现（分别最早在4天和9天），并在100天时达到平台期。海马区CA3中细胞丢失程度较高的动物慢性癫痫发作的起始较晚（r = 0.83，p < 0.0005），这表明CA3是癫痫传播的途径之一。这些结果表明，慢性癫痫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、颗粒上层和颗粒内苔藓纤维发芽、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。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所必需的，但过多的细胞丢失可能会阻碍癫痫发生。
