Neurogenesis and aberrant neuronal reorganization in the hippocampus of the animal models of epilepsy

本研究采用三甲基锡（TMT）诱导的癫痫模型和自发性癫痫模型（Noda epileptic rat：NER），观察癫痫发作后海马神经发生的变化。TMT治疗后5-7 d齿状回神经发生明显减少，14-28 d恢复到基础水平。相比之下，新产生的神经元的数量显着减少，在年轻的海马（7 W）NERs与他们的控制相比，而没有显着差异，在成年人（12 W）NERs和他们的控制之间观察到神经原性标记物的免疫染色。在此基础上，我们进一步研究了神经肽和神经免疫系统在这些模型中对神经发生的影响。用甲吡酮处理TMT给药的大鼠，以暂时抑制循环皮质酮。甲吡酮诱导的病理性低水平皮质酮在治疗后3-5 d未改变TMT对海马的损伤，但随后在给药后14 d增加了海马神经发生。TMT处理后4 d，肝门区NPY免疫反应增强，16 d后逐渐降低至对照组以下。TMT处理后2天，门部NPY mRNA信号增加。在NER中，癫痫发作后齿状回的NPY免疫反应性持续升高，而NPY mRNA瞬时增加（24小时内）。这些结果提示，神经免疫系统和神经肽在不同发病机制的癫痫发作后的神经发生调控中可能起重要作用。

We investigated the changes in hippocampal neurogenesis after the epileptic seizures using several models of epilepsy ; trimethyltin (TMT)-induced seizure model and spontaneous epileptic strain (Noda epileptic rat : NER). After TMT administration, neurogenesis was significantly decreased in the dentate gyrus at 5-7 d after treatment, and subsequently returned to basal level at 14-28 d. In comparison, the number of newly generated neurons was significantly decreased in the hippocampus of young (7W) NERs compared with their controls, while no significant differences in immunostaining of neurogenic markers were observed between adult (12W) NERs and their controls. Further, we evaluated the effect of neuropeptides and neural immune system on neurogenesis in these models. TMT-administered rats were treated with metyrapone in order to transiently suppress circulating corticosterone. The pathologically low levels of corticosterone induced by metyrapone did not alter the hippocampal damage of TMT at 3-5 d after treatment, however, subsequently increased hippocampal neurogenesis at 14 d after TMT administration. NPY-immunoreactivity increased at 4 d after TMT treatment in the hilus, and progressively decreased to a level below controls at 16 d after treatment. NPY mRNA signals increased in the hilus for 2 days after TMT treatment. In NER, NPY immunoreactivity in the dentate gyrus was continuously elevated, while NPY mRNA increased transiently (within 24 h) after a seizure. These results suggest that both neural immune system and neuropeptides may play a crucial role for the control of neurogenesis after epileptic seizures with different pathogenesis.