André Véronique M, Wu Nanping, Yamazaki Irene, Nguyen Snow T, Fisher Robin S, Vinters Harry V, Mathern Gary W, Levine Michael S, Cepeda Carlos
Mental Retardation Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
J Neuropathol Exp Neurol. 2007 Jun;66(6):491-504. doi: 10.1097/01.jnen.0000240473.50661.d8.
A defining histopathologic feature of Taylor-type cortical dysplasia (CD) is the presence of cytomegalic neurons and balloon cells. Most cytomegalic neurons appear to be pyramidal-shaped and glutamatergic. The present study demonstrates the presence of cytomegalic GABAergic interneurons in a subset of pediatric patients with severe CD. Cortical tissue samples from children with mild, severe, and non-CD pathologies were examined using morphologic and electrophysiologic techniques. By using in vitro slices, cytomegalic cells with characteristics consistent with interneurons were found in 6 of 10 patients with severe CD. Biocytin labeling demonstrated that cytomegalic interneurons had more dendrites than normal-appearing interneurons. Whole-cell patch clamp recordings showed that cytomegalic interneurons had increased membrane capacitance and time constant compared with normal-appearing interneurons. They also displayed signs of cellular hyperexcitability, evidenced by increased firing rates, decreased action potential inactivation, and the occurrence of spontaneous membrane depolarizations. Single-cell reverse transcription-polymerase chain reaction and immunohistochemistry for GABAergic markers provided further evidence that these cells were probably cytomegalic interneurons. The pathophysiologic significance of GABAergic cytomegalic interneurons in severe CD tissue is unknown, but they could inhibit glutamatergic cytomegalic pyramidal neurons, or contribute to the synchronization of neuronal networks and the propagation of ictal activity in a subset of pediatric patients with severe CD.
泰勒型皮质发育异常（CD）的一个典型组织病理学特征是存在巨细胞神经元和气球样细胞。大多数巨细胞神经元似乎呈金字塔形且为谷氨酸能神经元。本研究证实在一部分重度CD的儿科患者中存在巨细胞GABA能中间神经元。使用形态学和电生理学技术检查了患有轻度、重度和非CD病变的儿童的皮质组织样本。通过使用体外脑片，在10例重度CD患者中的6例中发现了具有与中间神经元一致特征的巨细胞。生物素标记显示，巨细胞中间神经元的树突比外观正常的中间神经元更多。全细胞膜片钳记录显示，与外观正常的中间神经元相比，巨细胞中间神经元的膜电容和时间常数增加。它们还表现出细胞过度兴奋的迹象，表现为放电频率增加、动作电位失活减少以及自发膜去极化的发生。单细胞逆转录聚合酶链反应和GABA能标志物的免疫组织化学提供了进一步证据，表明这些细胞可能是巨细胞中间神经元。重度CD组织中GABA能巨细胞中间神经元的病理生理意义尚不清楚，但它们可能抑制谷氨酸能巨细胞锥体神经元，或有助于一部分重度CD儿科患者的神经网络同步和发作期活动的传播。
