Hippocampus and epilepsy: Findings from human tissues.
Hippocampus and epilepsy: Findings from human tissues.
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DOI：
10.1016/j.neurol.2015.01.563
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发表时间：
2015-03
影响因子：
3
通讯作者：
Miles R
中科院分区：
文献类型：
--
作者：
Huberfeld G;Blauwblomme T;Miles R
手术切除致痫区是治疗几种癫痫综合征的有效方法。该手术为研究耐药部分癫痫综合征的活体组织病理活动提供了机会，包括(1)颞叶癫痫伴海马硬化，(2)皮质发育不良，(3)与肿瘤相关的癫痫和(4)发育畸形。这些综合征患者的组织切片保留了功能性神经网络，并可能产生癫痫活动。该组织中细胞的特性可能不会发生很大变化，但兴奋性突触传递往往增强，gaba能抑制得以保留。典型的癫痫活动不是由新皮质自发产生的，不管是否发育不良，而是由惊厥引起的。在新皮层中启动的临界放电依赖于gaba能信号和细胞外钾的增加。相反，颞叶癫痫伴海马硬化症患者的组织产生自发性的间期样活动。这种活动不是在海马体中开始的，而是在一个投射到内嗅皮层的输出区域——枕下。间期事件似乎是由gaba能细胞触发的，矛盾的是，它激发了大约20%的丘下锥体细胞，同时抑制了大多数细胞。因此间期放电依赖于gaba能和谷氨酸能信号。GABA的去极化作用依赖于某些潜细胞中氯离子水平的病理升高，类似于发育不成熟细胞。这种缺陷是由调节细胞内氯离子浓度的共转运蛋白NKCC1和挤出体KCC2的表达紊乱引起的。利尿剂布美他胺阻断NKCC1的作用，恢复细胞内氯化物，从而超极化gaba能作用，从而抑制间期活性。
Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity.
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