Leung Amanda, Ahn Sandra, Savvidis George, Kim Yeachan, Iskandar Danielle, Luna Maria Jose, Kim Kwang-Soo, Cunningham Miles, Chung Sangmi
Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
Epilepsy Res. 2015 Jan;109:114-8. doi: 10.1016/j.eplepsyres.2014.10.016. Epub 2014 Nov 6.
Temporal lobe epilepsy (TLE) has been modeled in mice using pilocarpine induction, with variable results depending on specific strains. To allow efficient xenotransplantation for the purpose of optimizing potential cell-based therapy of human TLE, we have determined the optimal dosing strategy to produce spontaneous recurring seizures in immunodeficient NodScid mice. Multiple 100mg/kg injections of pilocarpine have been shown to be more effective than single 300-400mg/kg injections for inducing spontaneous seizures in NodScid mice. Under our optimal conditions, 88.1 ± 2.9% of the mice experienced status epilepticus (SE) with a survival rate of 61.8 ± 5.9%. Surviving SE mice displayed spontaneous recurrent seizures at a frequency of 2.8 ± 0.9 seizures/day for a duration of 41.1 ± 3.5s. The widely used method of a single injection of pilocarpine was significantly less efficient in inducing seizures in NodScid mice. Therefore, we have determined that a multiple injection "ramping up" of 100mg/kg of pilocarpine is optimal for inducing TLE-like spontaneous seizures in NodScid mice. Using this method, mice with SE efficiently developed SRS and expressed mossy fiber sprouting, a signature histopathological feature of TLE.
颞叶癫痫（TLE）已通过毛果芸香碱诱导在小鼠中建模，结果因特定品系而异。为了实现高效的异种移植，以优化针对人类TLE的潜在细胞疗法，我们确定了在免疫缺陷的NodScid小鼠中产生自发性复发性癫痫发作的最佳给药策略。已证明多次注射100mg/kg毛果芸香碱比单次注射300 - 400mg/kg在诱导NodScid小鼠自发性癫痫发作方面更有效。在我们的最佳条件下，88.1±2.9%的小鼠经历了癫痫持续状态（SE），存活率为61.8±5.9%。存活的SE小鼠表现出自发性复发性癫痫发作，频率为2.8±0.9次/天，持续时间为41.1±3.5秒。广泛使用的单次注射毛果芸香碱的方法在诱导NodScid小鼠癫痫发作方面效率明显较低。因此，我们确定多次注射100mg/kg毛果芸香碱的“逐步增加”方法对于在NodScid小鼠中诱导类似TLE的自发性癫痫发作是最佳的。使用这种方法，患有SE的小鼠有效地发展出SRS并表现出海马苔藓纤维发芽，这是TLE的标志性组织病理学特征。
