In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. Parvalbumin-immunoreactive cells were observed mostly in subgranular location in the dentate hilus in controls, in tumor-induced TLE, in malformation of cortical development and in MR-negative cases. In patients with HS, significant decrease in the number of hilar parvalbumin-immunoreactive cells and large numbers of ectopic parvalbumin-containing neurons were detected in the dentate gyrus’ molecular layer. The ratio of ectopic/normally-located cells was significantly higher in HS than in other TLE groups. In patients with HS, robust sprouting of parvalbumin-immunoreactive axons were frequently visible in the molecular layer. The extent of sprouting was significantly higher in TLE patients with HS than in other groups. Strong sprouting of parvalbumin-immunoreactive axons were frequently observed in patients who had childhood febrile seizure. Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.

在本研究中，我们检查了具有不同病因的耐治疗性颞叶癫痫（TLE）患者的手术切除组织的齿状回中的小白蛋白免疫反应性细胞和轴突。根据MRI结果，分为五组患者：（1）海马硬化（HS），（2）皮质发育畸形，（3）皮质发育+ HS畸形，（4）肿瘤引起的TLE，（5） MRI结果阴性的患者。四个对照样品也包括在研究中。小白蛋白免疫反应性细胞多见于对照组齿状的颗粒下位置，肿瘤诱导的TLE，皮质发育畸形和MR阴性病例。在HS患者中 齿状回分子层中肺门小白蛋白免疫反应性细胞数量显着减少，并且含有大量异位小白蛋白的神经元。HS中异位/正常定位细胞的比例明显高于其他TLE组。在HS患者中，小分子白蛋白免疫反应性轴突的旺盛发芽在分子层中经常可见。TLE HS患者的发芽程度明显高于其他组。在患有儿童高热惊厥的患者中经常观察到小白蛋白免疫反应性轴突的强烈萌芽。发现轴突的发芽水平与异位/正常定位的含有小白蛋白的细胞的比例之间存在显着的相关性。电子显微镜显示，发芽的小白蛋白免疫反应性轴突终止于近端和远端树突状干以及颗粒细胞的树突状棘。我们的结果表明，HS中小白蛋白免疫反应性神经元的靶标分布发生改变，这有助于TLE中已知的突触重塑。