Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex.
Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex.
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DOI：
10.1111/j.1460-9568.2010.07179.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Holmes GL
中科院分区：
文献类型：
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作者：
Isaeva E;Isaev D;Savrasova A;Khazipov R;Holmes GL
新生儿癫痫发作与神经系统不良后果的高可能性相关，包括智力迟钝、行为障碍和癫痫。早期癫痫发作通常涉及新皮层，新生儿后癫痫通常是新皮层起源。然而，我们对新生儿癫痫发作对新皮质功能的影响的理解是有限的。在本研究中，我们发现氟醚诱导的新生儿癫痫发作导致新皮层对癫痫样活动的易感性显著增强。这种变化发生在最后一次诱发癫痫发作数周后研究的幼鼠和首次癫痫发作数月后研究的成年大鼠。新生儿癫痫发作导致自发性抑制性突触后电流的振幅和微型抑制性突触后电流的频率降低，而自发性兴奋性突触后电流（sEPSCs）的振幅和频率以及体感觉皮层第2/3层锥体细胞的微型兴奋性突触后电流（mEPSCs）的频率显著增加。选择性n-甲基-d-天冬氨酸（NMDA）受体拮抗剂d-2-氨基-5-卵磷脂消除了对照组和氟基组中sEPSCs和mEPSCs的振幅和频率差异，表明NMDA受体对复发性新生儿癫痫大鼠的兴奋性增强有重要作用。综上所述，我们的研究结果表明，婴儿期反复发作会导致新皮质兴奋性的持续增强。
Neonatal seizures are associated with a high likelihood of adverse neurological outcomes, including mental retardation, behavioral disorders, and epilepsy. Early seizures typically involve the neocortex, and post-neonatal epilepsy is often of neocortical origin. However, our understanding of the consequences of neonatal seizures for neocortical function is limited. In the present study, we show that neonatal seizures induced by flurothyl result in markedly enhanced susceptibility of the neocortex to seizure-like activity. This change occurs in young rats studied weeks after the last induced seizure and in adult rats studied months after the initial seizures. Neonatal seizures resulted in reductions in the amplitude of spontaneous inhibitory postsynaptic currents and the frequency of miniature inhibitory postsynaptic currents, and significant increases in the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal cells of layer 2/3 of the somatosensory cortex. The selective N-methyl-d-aspartate (NMDA) receptor antagonist d-2-amino-5-phosphon-ovalerate eliminated the differences in amplitude and frequency of sEPSCs and mEPSCs in the control and flurothyl groups, suggesting that NMDA receptors contribute significantly to the enhanced excitability seen in slices from rats that experienced recurrent neonatal seizures. Taken together, our results suggest that recurrent seizures in infancy result in a persistent enhancement of neocortical excitability.