Microanatomy of the dysplastic neocortex from epileptic patients
Microanatomy of the dysplastic neocortex from epileptic patients
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DOI：
10.1093/brain/awh331
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发表时间：
2005-01-01
期刊：
影响因子：
14.5
通讯作者：
DeFelipe, J
中科院分区：
文献类型：
--
作者：
Alonso-Nanclares, L;Garbelli, R;DeFelipe, J
局灶性皮质发育不良（FCD）是一种以新皮质发育异常为特征的病理学。事实上，皮质套中的多种异常都与这种病理学相关，包括细胞结构的改变以及白质中畸形神经元、气球细胞和异位神经元的存在。 FCD 通常与癫痫相关，因此我们研究了从三名继发于皮质发育不良的顽固性癫痫受试者身上切除的皮质组织的超微结构，以使用相关的光和电子显微镜方法来识别突触回路可能的改变。虽然在该组织中发现的气球细胞似乎没有接受突触接触，但白质中的异位神经元异常大，并且被对钙结合蛋白小白蛋白产生免疫反应的肥大篮结构包围。此外，这些篮子结构与这些巨大异位神经元的体细胞和树突近端部分形成对称（抑制性）突触。定量分析显示，在发育不良的组织中，兴奋性和抑制性突触的密度与正常相邻皮层的密度不同。观察到突触密度的增加和减少，以及兴奋性和抑制性突触比例的变化。然而，我们无法在同一患者或不同患者之间建立共同的变化模式。这些结果表明皮质发育不良导致兴奋性和抑制性突触回路的多种变化。我们讨论这些改变与癫痫之间的可能关系，同时考虑到可能的局限性，这些局限性妨碍了将结果外推到整个新皮质发育不良的癫痫患者群体。
Focal cortical dysplasia (FCD) is a pathology that is characterized by the abnormal development of the neocortex. Indeed, a wide range of abnormalities in the cortical mantle have been associated with this pathology, including cytoarchitectonic alterations and the presence of dysmorphic neurons, balloon cells and ectopic neurons in the white matter. FCD is commonly associated with epilepsy, and hence we have studied the ultrastructure of cortical tissue resected from three subjects with intractable epilepsy secondary to cortical dysplasia to identify possible alterations in synaptic circuitry, using correlative light and electron microscopic methods. While the balloon cells found in this tissue do not appear to receive synaptic contacts, the ectopic neurons in the white matter were abnormally large and were surrounded by hypertrophic basket formations immunoreactive for the calcium-binding protein parvalbumin. Furthermore, these basket formations formed symmetrical (inhibitory) synapses with both the somata and the proximal portion of the dendrites of these giant ectopic neurons. A quantitative analysis revealed that in the dysplastic tissue, the density of excitatory and inhibitory synapses was different from that of the normal adjacent cortex. Both increases and decreases in synaptic density were observed, as well as changes in the proportion of excitatory and inhibitory synapses. However, we could not establish a common pattern of changes, either in the same patients or between different patients. These results suggest that cortical dysplasia leads to multiple changes in excitatory and inhibitory synaptic circuits. We discuss the possible relationship between these alterations and epilepsy, bearing in mind the possible limitations that preclude the extrapolation of the results to the whole population of epileptic patients with dysplastic neocortex.