Liu Z, Nagao T, Desjardins G C, Gloor P, Avoli M
Montreal Neurological Institute, McGill University, QC, Canada.
Epilepsy Res. 1994 Mar;17(3):237-47. doi: 10.1016/0920-1211(94)90054-x.
Systemic administration of the cholinergic agonist pilocarpine (350-400 mg/kg, i.p.) to rats induces acute behavioral and EEG status epilepticus followed by apparent complete neurological recovery. In rats receiving higher doses of pilocarpine (i.e., 380-400 mg/kg), recurrent seizures reappear 2-2.5 weeks later and continue to occur as long as the rats are kept alive. Stereological estimates of neurons in regions CA1, CA3 and the dentate granule cell layer in the dorsal hippocampus show a dose-dependent neuronal loss in the CA3 and CA1 subregions. The granule cell layer of the dentate gyrus is not affected. No progressive neuronal loss was observed in the regions studied after 3, 6 and 12 weeks during which the animals displayed spontaneous recurrent seizures. The temporal profile of the epileptic condition induced by pilocarpine and the resulting pattern of neuronal loss in the rat hippocampus are similar to those seen in many cases of human temporal lobe epilepsy. The neuronal loss is dose-dependent and primarily results from the acute pilocarpine-induced seizures as chronic seizures do not produce any measurable additional cell loss in the regions examined in the experimental model used in this study.
向大鼠腹腔注射胆碱能激动剂毛果芸香碱（350 - 400毫克/千克）进行全身给药，会诱发急性行为和脑电图癫痫持续状态，随后大鼠的神经系统明显完全恢复。在接受较高剂量毛果芸香碱（即380 - 400毫克/千克）的大鼠中，2 - 2.5周后会再次出现复发性癫痫发作，只要大鼠存活就会持续发作。对背侧海马体中CA1、CA3区域和齿状颗粒细胞层的神经元进行体视学估计，结果显示CA3和CA1子区域存在剂量依赖性神经元损失。齿状回的颗粒细胞层未受影响。在动物出现自发性复发性癫痫发作的3、6和12周期间，在所研究的区域未观察到进行性神经元损失。毛果芸香碱诱发的癫痫状况的时间特征以及大鼠海马体中由此产生的神经元损失模式，与人类颞叶癫痫的许多病例中所观察到的情况相似。神经元损失具有剂量依赖性，主要是由急性毛果芸香碱诱发的癫痫发作导致的，因为在本研究使用的实验模型中，慢性癫痫发作在所检查的区域并未导致任何可测量的额外细胞损失。
