Department of Neurosciences (Divisions of Neurology and Neurosurgery), Medical University of South Carolina, Charleston, SC 29425, USA.
Neuroscience. 2012 Sep 18;220:237-46. doi: 10.1016/j.neuroscience.2012.06.002. Epub 2012 Jun 12.
Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Previous research has demonstrated several trends in human tissue that, undoubtedly, contribute to the development and progression of TLE. In this study we examined resected human hippocampus tissue for a variety of changes including gliosis that might contribute to the development and presentation of TLE. The study subjects consisted of six TLE patients and three sudden-death controls. Clinicopathological characteristics were evaluated by H&E staining. Immunohistological staining and Western blotting methods were used to analyze the samples. Neuronal hypertrophy was observed in resected epileptic tissue. Immunohistological staining demonstrated that activation of astrocytes was significantly increased in epileptic tissue as compared to corresponding regions of the control group. The Western blot data also showed increased CX43 and AQP4 in the hippocampus and downregulation of Kir4.1, α-syntrophin, and dystrophin, the key constituents of AQP4 multi-molecular complex. These tissues also demonstrated changes in inflammatory factors (COX-2, TGF-β, NF-κB) suggesting that these molecules may play an important role in TLE pathogenesis. In addition we detected increases in metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and kainic acid receptor subunits KA1 (Grik4) and KA2 (Grik5) in patients' hippocampi. We noted increased expression of the α1c subunit comprising class C L-type Ca(2+) channels and calpain expression in these tissues, suggesting that these subunits might have an integral role in TLE pathogenesis. These changes found in the resected tissue suggest that they may contribute to TLE and that the kainic acid receptor (KAR) and deregulation of GluR2 receptor may play an important role in TLE development and disease course. This study identifies alterations in number of commonly studied molecular targets associated with astrogliosis, cellular hypertrophy, water homeostasis, inflammation, and modulation of excitatory neurotransmission in hippocampal tissues from TLE patients.
颞叶癫痫（TLE）是最常见的局灶性癫痫。先前的研究已经证明了人类组织中的几种趋势，这些趋势无疑有助于 TLE 的发展和进展。在这项研究中，我们检查了切除的人类海马组织，以寻找包括胶质增生在内的各种变化，这些变化可能有助于 TLE 的发展和表现。研究对象包括 6 名 TLE 患者和 3 名猝死对照者。通过 H&E 染色评估临床病理特征。免疫组织化学染色和 Western blot 方法用于分析样本。在切除的癫痫组织中观察到神经元肥大。免疫组织化学染色表明，与对照组相应区域相比，癫痫组织中星形胶质细胞的激活显著增加。Western blot 数据还显示海马中 CX43 和 AQP4 增加，以及 Kir4.1、α-突触核蛋白和营养不良蛋白的下调，AQP4 多分子复合物的关键成分。这些组织还表现出炎症因子（COX-2、TGF-β、NF-κB）的变化，表明这些分子可能在 TLE 发病机制中发挥重要作用。此外，我们在患者海马中检测到代谢型谷氨酸受体（mGluR）2/3、mGluR5 和红藻氨酸受体亚基 KA1（Grik4）和 KA2（Grik5）的增加。我们注意到这些组织中 C 型 L 型钙（Ca2+）通道的α1c 亚基和钙蛋白酶的表达增加，表明这些亚基可能在 TLE 发病机制中具有重要作用。在切除组织中发现的这些变化表明它们可能有助于 TLE，而红藻氨酸受体（KAR）和 GluR2 受体失活可能在 TLE 的发展和病程中起重要作用。本研究确定了 TLE 患者海马组织中与星形胶质细胞增生、细胞肥大、水稳态、炎症和兴奋性神经递质调节相关的常见研究分子靶标的数量变化。
