Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, Guizhou, Guiyang City, China.
Public Health School, Guizhou Medical University, Guizhou, Guiyang City, China.
World Neurosurg. 2019 Aug;128:e1-e11. doi: 10.1016/j.wneu.2019.01.245. Epub 2019 Feb 18.
This study aimed to explore whether intrahippocampal transplantation of GABAergic neurons generated in vitro ameliorated seizures and epileptiform discharges via increasing γ-aminobutyric acid (GABA)-associated inhibition mediated by the addition of new GABAergic neurons.
Neural stem cells (NSCs) isolated from newborn rats were induced and differentiated into GABAergic neurons. A total of 36 Pilocarpine-induced pharmacoresistant epileptic rats were divided into 3 groups: PBS (phosphate-buffered saline) group, NSCs group, and GABAergic neurons group (GABA group), with an additional 10 normal rats used (normal rat control group). The effects of grafting on spontaneous recurrent seizures (SRS) were examined and hippocampal GABA content was measured after grafting.
In the GABA group, the frequency of electroencephalography decreased significantly compared with the PBS group (P < 0.001), but there was no significant difference between the GABA group and NSCs group. Compared with the PBS group, the overall frequency and duration of SRS significantly decreased in the transplantation group, especially in the GABA group (P < 0.01). The number of GABAergic neurons was highest in the GABA group compared with the other groups (P < 0.001). Furthermore, hippocampal GABA concentrations significantly increased in the GABA group.
We show that GABAergic neurons generated in vitro from NSCs and grafted into the hippocampi of chronically epileptic rats can significantly reduce the frequency of electroencephalography and frequency and duration of SRS via increasing GABA-associated inhibition mediated by the addition of new GABAergic neurons.
本研究旨在探讨体外生成的 GABA 能神经元内海移植是否通过增加新 GABA 能神经元介导的 GABA 相关抑制来改善癫痫发作和癫痫样放电。
从新生大鼠中分离神经干细胞（NSCs），并诱导分化为 GABA 能神经元。将 36 只匹罗卡品诱导的耐药性癫痫大鼠分为 PBS（磷酸盐缓冲液）组、NSCs 组和 GABA 能神经元组（GABA 组），另外 10 只正常大鼠作为正常大鼠对照组。移植后检测自发复发癫痫（SRS）的影响，并测量海马 GABA 含量。
在 GABA 组中，与 PBS 组相比，脑电图频率显著降低（P < 0.001），但与 NSCs 组相比无显著差异。与 PBS 组相比，移植组的 SRS 总频率和持续时间明显降低，尤其是在 GABA 组（P < 0.01）。与其他组相比，GABA 组中 GABA 能神经元数量最高（P < 0.001）。此外，GABA 组海马 GABA 浓度显著升高。
我们表明，从 NSCs 体外生成的 GABA 能神经元并移植到慢性癫痫大鼠的海马中，可以通过增加新 GABA 能神经元介导的 GABA 相关抑制来显著降低脑电图频率以及 SRS 的频率和持续时间。
