A study on the molecular pathomechanisms underflying intractable epilepsy

1.对125例耐药难治性癫痫患者进行了组织病理学观察。内侧颞叶皮质发育不良(I级)是最常见的异常(66例)。癫痫发作和手术的平均年龄分别为12.2岁和31.4岁。在所有病例中，胶质纤维酸性蛋白阳性反应性星形胶质细胞存在于受累皮质和皮质下白质中。共32例患者进行了海马区检查：海马区硬化症的组织学严重程度与皮质发育不良的严重程度之间无相关性。我们报告了一例双侧脑室周围结节异位的尸检病例的组织病理学特征，在该病例中我们发现了一种新的外显子11(Val528Met)细丝蛋白1突变。我们利用DNA阵列技术比较了人脑三个新皮质亚区：前额叶皮质(46区)、运动皮质(4区)和视觉皮质(17区)的mRNA表达谱。对死后大脑中高质量mRNA的大阵列分析表明，不同皮质区域的表达谱几乎相似：在1088个已知基因中，只有6个基因的表达存在显著差异(2倍)。随着样本数量的增加，RT-PCR研究证实，只有膜联蛋白II和早期生长反应蛋白1这两个基因在不同区域的表达差异2倍，而其他基因的表达显示出很大的个体差异。这些结果表明，在总基因表达谱水平上，人类的整个新皮质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.