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GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset
Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2020-09-01 , DOI: 10.3389/fncel.2020.562811
Jyotirmoy Banerjee , Soumil Dey , Aparna Banerjee Dixit , Ramesh Doddamani , Meher Chand Sharma , Ajay Garg , P. Sarat Chandra , Manjari Tripathi

Enhanced spontaneous GABAA receptor activity is associated with focal cortical dysplasia (FCD), a developmental malformation of the cerebral cortex. Clinical manifestations in FCD vary with age at epilepsy onset with a more favorable prognosis in patients with late-onset (LO) compared to that in cases with early-onset (EO). This study was designed to test the hypothesis in FCD that spontaneous GABAA receptor-mediated epileptogenicity depends on the age at epilepsy onset and varies between patients with early and late-onset age in FCD. To this end, brain specimens were obtained from the maximal spiking region (MAX) and minimal spiking region (MIN) of the epileptic foci of EO (n = 14, mean age = 10.6 ± 2.9 years) and LO (n = 10, mean age = 27 ± 5.6 years) patients undergoing electrocorticography (ECoG) guided surgery. The whole-cell patch-clamp technique was used to record spontaneous GABAergic currents from normal-looking pyramidal neurons in slice preparations of resected brain samples. We detected higher frequency and amplitude of GABAergic events in MAX samples compared to MIN samples of LO patients, while they were comparable in MIN and MAX samples of EO patients. Further GABAergic activity in the MIN and MAX samples of EO patients was higher than the MIN samples of LO patients. This suggests that in LO patients, GABAA receptor-mediated epileptogenicity is confined only to the high spiking areas, but in EO patients, it affects low spiking regions as well.



中文翻译:

局灶性皮质发育不良(FCD)中GABAA受体介导的癫痫发生取决于癫痫发作的年龄。

自发性GABA A受体活性增强与局灶性皮质发育不良(FCD)有关,后者是大脑皮质的发育畸形。FCD的临床表现随癫痫发作的年龄而变化,与早期发作(EO)的患者相比,晚期发作(LO)的患者预后更好。这项研究旨在检验FCD的假说,即自发GABA A受体介导的癫痫发生取决于癫痫发作的年龄,并且在FCD发病年龄的早晚之间有所不同。为此,从EO癫痫灶的最大峰值区域(MAX)和最小峰值区域(MIN)获得了大脑标本。ñ = 14,平均年龄= 10.6±2.9岁)和LO(ñ= 10,平均年龄= 27±5.6岁)接受皮质脑电图(ECoG)引导手术的患者。全细胞膜片钳技术用于记录切除的脑样本切片制剂中外观正常的锥体神经元的自发GABA能电流。与LO患者的MIN样本相比,我们在MAX样本中检测到更高的GABA能事件频率和幅度,而在EO患者的MIN和MAX样本中,它们具有可比性。在EO患者的MIN和MAX样本中,进一步的GABA能活性高于LO患者的MIN样本。这表明在LO患者中,GABA A受体介导的癫痫发生仅限于高刺区域,而在EO患者中,它也影响低刺区域。

更新日期:2020-09-30
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