A study on the molecular pathomechanisms underflying intractable epilepsy

1.本文对125例难治性耐药癫痫进行了组织病理学观察。颞叶内侧皮质发育不良（I级）是最常见的异常（66例）。癫痫发作和手术时的平均年龄分别为12.2岁和31.4岁。在所有病例中，胶质细胞酸性蛋白阳性反应星形胶质细胞存在于受影响的皮质以及皮质下白色物质。共检查32例海马：海马硬化的组织学严重程度与皮质发育不良的组织学严重程度无相关性.我们报告了一例双侧脑室周围结节性异位症的尸检病例的组织病理学特征，该病例伴有广泛的肾小球样微血管异常和大脑皮质发育异常的细胞结构，我们在其中发现了一种新的11号外显子（Val 528 Met）细丝蛋白1突变。我们采用DNA阵列技术比较了人类大脑的三个新皮层亚区：前额叶皮层（46区），运动皮层（4区）和视觉皮层（17区）的mRNA表达谱。对来自死后大脑的高质量mRNA的宏阵列分析显示，不同皮层区域的表达谱几乎相似：1088个已知基因中只有6个在其表达中表现出显著差异（>2倍）。RT-PCR研究的样品数量增加证实，只有两个基因，膜联蛋白II和早期生长反应蛋白1的表达，不同的区域之间的2倍，而其他的expression表现出很大的个体间差异。这些结果表明，在基因表达谱的水平上，人类的整个新皮层比我们预期的更均匀。

1. We carried out the histopathological observations in 125 patients with pharmacoresistant intractable epilepsy. Cortical dysplasia (Grade I) in the medial temporal lobe was found to be the most frequent abnormality (66 cases). The mean ages at onset of seizure and at surgery were 12.2 years and 31.4 years, respectively. In all the cases, glial fibrillary acidic protein-positive reactive astrocytes were present in the affected cortex as well as in the subcortical white matter. The hippocampus was examined in a total of 32 cases : there were no correlation between histological severity of hippocampal sclerosis and that of cortical dysplasia.2. We reported the histopathological features of an autopsy case of bilateral periventricular nodular heterotopia with widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex, in whom we found a novel exon 11 (Val528Met) filamin 1 mutation.3. We employed the DNA array technique to compare the mRNA expression profiles of three neocortical subregions of the human brain : prefrontal cortex (Area 46), motor cortex (Area 4) and visual cortex (Area 17). The macroarray analysis on high quality mRNA from postmortem brains revealed that the expression profiles of the different cortical areas are almost similar : only six out of 1088 known genes exhibited significant differences (>2-fold) in their expression. RT-PCR studies with an increased number of samples confirmed that expression of only two genes, annexin II and early growth response protein 1, varied by 2-fold among the regions, whereas exoression of the others showed large inter-individual difference. These results suggest that the whole neocortex of humans is more homogeneous than we expected at the level of gross gene expression profiles.