Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors.
Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors.
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DOI：
10.1016/j.neuroscience.2012.06.002
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发表时间：
2012-09-18
期刊：
影响因子：
3.3
通讯作者：
Banik, N. L.
中科院分区：
文献类型：
--
作者：
Das, A.;Wallace, G. C.;Holmes, C.;McDowell, M. L.;Smith, J. A.;Marshall, J. D.;Bonilha, L.;Edwards, J. C.;Glazier, S. S.;Ray, S. K.;Banik, N. L.
颞叶癫痫（TLE）是局灶性癫痫最常见的形式。先前的研究已经证明了人体组织中的几种趋势，毫无疑问，这些趋势有助于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的各种变化，包括胶质增生，可能有助于TLE的发展和介绍。研究对象包括6例TLE患者和3例猝死对照。H&E染色评价临床病理特征。采用免疫组织化学染色和Western blotting方法对标本进行分析。在切除的癫痫组织中观察到神经元肥大。免疫组化染色显示，与对照组相应区域相比，癫痫组织中星形胶质细胞的活化显著增加。蛋白质印迹数据还显示，海马中的CX43和AQP 4增加，Kir4.1、α-syntrophin和dystrophinin下调，它们是AQP 4多分子复合物的关键成分。这些组织还显示炎性因子（考克斯-2、TGF-β、NF κ B）的变化，表明这些分子可能在TLE发病机制中起重要作用。此外，我们检测到代谢型谷氨酸受体（mGluR）2/3，mGluR 5和红藻氨酸受体亚单位KA 1（Grik 4）和KA 2（Grik 5）在患者的大脑中增加。我们注意到这些组织中包含C类L型Ca 2+通道和钙蛋白酶的α1c亚基表达增加，表明这些亚基可能在TLE发病机制中起着不可或缺的作用。在切除的组织中发现的这些变化表明它们可能有助于TLE，并且红藻氨酸受体（KAR）和GluR 2受体的失调可能在TLE的发展和疾病过程中起重要作用。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、炎症和兴奋性神经传递调节相关的一些常用研究分子靶点的改变。
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 may contribute to the development and presentation of TLE. The study subjects consisted of 6 TLE patients and 3 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 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 dystrophinin, which are the key constituents of AQP4 multi-molecular complex. These tissues also demonstrated changes in inflammatory factors (COX-2, TGF-β, NFkB) 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 Ca2+ channels and calpain expression in these tissues, suggesting that these subunits may 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 tissue from TLE patients.
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影响因子：
5.3
作者：
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通讯作者：
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