Decreased time constant in hippocampal dentate granule cells in pilocarpine-treated rats with progressive seizure frequencies.
Decreased time constant in hippocampal dentate granule cells in pilocarpine-treated rats with progressive seizure frequencies.
复制标题
毛果芸香碱治疗的大鼠海马齿状颗粒细胞时间常数降低，癫痫发作频率进行性增加。
DOI：
10.1016/0006-8993(96)00118-7
复制
发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Isokawa,M
中科院分区：
文献类型：
--
作者：
Isokawa,M
谷氨酸介导的兴奋性毒性细胞损伤与癫痫有关。虽然证据积累长期急性癫痫发作导致明确的细胞损伤，兴奋性毒性是否参与慢性癫痫的自发性癫痫发作知之甚少。在本研究中，自发性癫痫发作的频率，独立于外源性施加的刺激，在匹鲁卡品模型中与海马过度兴奋的关系进行了研究。自发性癫痫发作的长期观察（12小时/天，持续120或280天）发现平均基础癫痫发作频率为0.11次癫痫发作/天± 0.03 S.E.M.。30只动物然而，在这些动物中的13只（n = 9）中，癫痫发作频率显著增加至2.57次癫痫发作/天± 0.25 S.E.M.。（范围从2-13次/天），并且该高频率发作期持续20-95天。在观察期结束时制备海马切片，用于胞外场反应和全细胞膜片钳记录。在从显示癫痫发作频率的大鼠制备的切片中，谷氨酸介导的兴奋性突触后反应在海马齿状颗粒细胞（DGCs）中延长，其中多个尖峰以更高的概率产生。这些细胞的平均时间常数较短（14.2 ms ± 2.1 S.E.M.，P < 0.01）与对照动物中的正常DGC（21.2 ms ± 3.7 S.E.M.）相比，提示在自发性癫痫发作的复发过程中可能发生了细胞结构的减少。这表明，正在进行的癫痫活动可以在自发性癫痫发作的复发过程中的频率进展，神经元变性可能伴随着自发性癫痫发作的频率增加，这是由谷氨酸受体的激活增加介导的。
Glutamate-mediated excitotoxic cell damage has been implicated in epilepsy. Although evidence accumulates for prolonged acute seizures resulting in unequivocal cell damage, whether excitotoxicity is involved in spontaneous seizures in chronic epilepsy is poorly understood. In the present study, a frequency of spontaneous seizures, independent of exogenously applied stimulus, was studied in relation to hippocampal hyperexcitability in the pilocarpine model. A long-term observation (12 h/day for 120 or 280 days) of spontaneous seizures identified an average basic seizure frequency of 0.11 seizures/day ± 0.03 S.E.M. in 30 animals. However, in 1 3 of these animals (n = 9), a seizure frequency significantly increased to 2.57 seizures/day ± 0.25 S.E.M. (ranging from 2–13 seizures/day) in 40–165 days, and this period of high frequency of seizures lasted for 20–95 days. Hippocampal slices were prepared at the end of the observation period for extracellular field responses and whole-cell patch clamp recordings. In slices that were prepared from rats that showed progressive frequencies of seizures, glutamate-mediated excitatory postsynaptic responses were prolonged in hippocampal dentate granule cells (DGCs) from which multiple spikes were generated in higher probability. Average time constant was shorter in these cells (14.2 ms ± 2.1 S.E.M., P < 0.01) compared with normal DGCs in control animals (21.2 ms ± 3.7 S.E.M.), suggesting that cell structural diminution possibly occurred during the recurrence of spontaneous seizures. It is suggested that on-going seizure activities could progress in frequency during the recurrence of spontaneous seizures, and neuronal degeneration might be accompanied with increasing frequencies of spontaneous seizures that were mediated by the increased activation of glutamate receptors.