Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures.
Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures.
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DOI：
10.1016/j.neuron.2009.08.022
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发表时间：
2009-09-10
期刊：
影响因子：
16.2
通讯作者：
Staley KJ
中科院分区：
文献类型：
--
作者：
Glykys J;Dzhala VI;Kuchibhotla KV;Feng G;Kuner T;Augustine G;Bacskai BJ;Staley KJ
新生儿癫痫发作的电临床分离是指没有临床表现的癫痫发作电图活动。苯巴比妥治疗后解离增加，从而增加GABAA受体（GABAAR）的电导。GABAAR活化的作用取决于细胞内Cl -浓度（[Cl -]i），该浓度由向内Cl -转运蛋白NKCC1和向外Cl -转运蛋白KCC2决定。在皮质区和皮质下区观察到的Cl -转运的不同成熟应该会改变gaba介导的抑制的效果。在围产期大鼠幼仔中，大多数丘脑神经元维持低[Cl−]i，并受到GABA的抑制。苯巴比妥抑制丘脑癫痫活动。大多数新皮质神经元维持较高的[Cl−]i，并被GABAAR激活。在NKCC1被阻断之前，苯巴比妥对新皮层的抗惊厥反应不显著。因此，氯离子转运的区域差异可能解释了为什么抗惊厥药不能抑制皮层中的癫痫发作活动，因为抗惊厥药阻断了癫痫发作活动通过皮层下网络的传递。
Electroclinical dissociation of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Dissociation increases after treatment with Phenobarbital, which increases the GABAA receptor (GABAAR) conductance. The effects of GABAAR activation depend on the intracellular Cl− concentration ([Cl−]i) that is determined by the inward Cl− transporter NKCC1 and the outward Cl− transporter KCC2. Differential maturation of Cl− transport observed in cortical vs. subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl−]i, and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl−]i, and were excited by GABAAR activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl− transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks.
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