Molecular Neuroanatomy and Pathogenesis Unit, IRCCS Foundation Neurological Institute Carlo Besta, Via Libero Temolo 4, Milan, Italy.
Epilepsia. 2013 Sep;54 Suppl 6:33-6. doi: 10.1111/epi.12272.
Focal cortical dysplasia (FCD) is a brain malformation associated with particularly severe drug-resistant epilepsy that often requires surgery for seizure control. The molecular basis for such enhanced propensity to seizure generation in FCD is not as yet elucidated. To investigate cellular and molecular bases of epileptogenic mechanisms and possible effect of severe epilepsy on the malformed cortex we have here performed a parallel analysis of a rat model of acquired cortical dysplasia previously established in our laboratory, i.e., the methylazoxymethanol/pilocarpine (MAM-PILO) rats, and surgical samples from patients with type IIB FCD. Data from the MAM-PILO rat model and human FCD samples reveal in both conditions: (1) that status epilepticus (SE) and/or seizures can further modify the cellular and molecular settings of the malformed cortex; (2) excitation/inhibition imbalance, and dysregulation of the N-methyl-d-aspartate/ membrane-associated guanylate kinase (NMDA/MAGUK) expression; (3) activation of cell death in neurons and glia. The data therefore highlight the mechanistic relevance of glutamate/NMDA hyperactivation in FCD epileptogenesis and suggest that epilepsy is a pathologic process capable of affecting structure and function of both neurons and glia.
局灶性皮质发育不良（FCD）是一种与特别严重的耐药性癫痫相关的脑畸形，通常需要手术控制癫痫发作。导致 FCD 中癫痫发作倾向增强的分子基础尚未阐明。为了研究致痫机制的细胞和分子基础以及严重癫痫对畸形皮质的可能影响，我们在这里对我们实验室先前建立的获得性皮质发育不良大鼠模型（即甲基乙基亚硝脲/毛果芸香碱（MAM-PILO）大鼠）和来自 IIB 型 FCD 患者的手术样本进行了平行分析。来自 MAM-PILO 大鼠模型和人类 FCD 样本的数据在两种情况下均显示：（1）癫痫持续状态（SE）和/或癫痫发作可进一步改变畸形皮质的细胞和分子环境；（2）兴奋/抑制失衡以及 N-甲基-D-天冬氨酸/膜相关鸟苷酸激酶（NMDA/MAGUK）表达的失调；（3）神经元和神经胶质细胞的细胞死亡激活。因此，这些数据突出了谷氨酸/NMDA 过度激活在 FCD 致痫中的机制相关性，并表明癫痫是一种能够影响神经元和神经胶质细胞结构和功能的病理过程。
