Hyperthermia induces epileptiform discharges in cultured rat cortical neurons
Hyperthermia induces epileptiform discharges in cultured rat cortical neurons
复制标题
高温诱导培养的大鼠皮层神经元发生癫痫样放电
DOI：
10.1016/j.brainres.2011.08.027
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发表时间：
2011-10-12
期刊：
影响因子：
2.9
通讯作者：
Xing, Guo-Gang
中科院分区：
文献类型：
--
作者：
Wang, Ying-Ying;Qin, Jiong;Xing, Guo-Gang
热性惊厥（FS）或发热性惊厥是儿童期最常见的癫痫发作形式。虽然单纯的FS通常被认为是良性的，但长期或复发的FS被认为会增加成年人继发颞叶癫痫（TLE）的风险。FS的病理生理学仍然是未知的。在这项研究中，通过使用全细胞膜片钳记录技术，我们证明了高温（39-40摄氏度）诱导的“发热性惊厥样事件”表达为自发的，复发性的，癫痫样放电（SRED），随后在培养的大鼠皮层神经元（7-14 DIV）的一系列持续去极化（SD）。SRED的特征是突然发展的，阵发性去极化移位（PDS）的膜电位与电描记癫痫发作的特征高频尖峰放电。此外，我们还发现高温可引起持续性神经元超兴奋，其内在的产电特征包括：1）去极化静息电位（RP），2）降低输入电阻（R-in.），3）降低输入电阻（R-in.）。3)自发动作电位的幅度、持续时间和后超极化（AHP）显著降低; 4）动作电位（AP）电流阈值（I-th）和电位阈值（TP）显著降低;和5）持续时间显著缩短，峰间间期（ISI）减少，诱发动作电位的放电频率增加。此外，我们目前的研究还表明，巴氯芬（100 μ M），一个特定的GABA（B）受体激动剂，显着抑制高血压诱导的神经元兴奋性和癫痫样放电在培养的皮层神经元。结果表明，高温可诱导癫痫样活动在培养的皮层神经元通过抑制GABA（B）受体介导的抑制，反过来导致发展的持续神经元的过度兴奋时，细胞遭受热损伤。本研究为热性惊厥发病机制的体外研究提供了一种新的细胞模型。(C)2011 Elsevier B. V.保留所有权利。
Febrile seizures (FS), or fever-induced seizures, are the most common form of seizures during childhood. Although simple FS are usually considered benign, prolonged or recurrent FS are proposed to increase the risk for developing subsequent temporal lobe epilepsy (TLE) in adults. The pathophysiology of FS is still largely unknown. In this study, by using whole-cell patch-clamp recording techniques, we demonstrated that hyperthermia (39-40 degrees C) induced a "febrile seizure-like event" expressed as spontaneous, recurrent, epileptiform discharges (SREDs) followed by a series of sustained depolarizations (SDs) in cultured rat cortical neurons (7-14 DIV). The SREDs were characterized by abruptly developing, paroxysmal depolarizing shifts (PDS) of membrane potential with high-frequency spike firing characteristic of electrographic seizures. Furthermore, we also found that hyperthermia induced persistent neuronal hyperexcitability as assessed by their intrinsic electrogenic characteristics which include: 1) depolarized resting potential (RP); 2) decreased input resistance (R-in.); 3) a marked decrease in amplitude, duration and afterhyperpolarization (AHP) of spontaneous action potentials; 4) a prominent reduction in action potential (AP) current threshold (I-th) and potential threshold (TP); and 5) a dramatic shortened duration, decreased inter-spike intervals (IS!), and increased firing frequency of evoked action potentials. Additionally, our present study also revealed that baclofen (100 mu M), a specific GABA(B) receptor agonist, significantly repressed the hyperthermia-induced neuronal hyperexcitability and epileptiform discharges in cultured cortical neurons. The results suggest that hyperthermia may induce epileptiform activities in cultured cortical neurons by suppression of the GABA(B) receptor-mediated inhibition, in turn leading to the development of persistent neuronal hyperexcitability when the cells suffered from heating insult. This study provides a novel cellular model for studying the pathogenetic mechanisms of febrile seizures in vitro. (C) 2011 Elsevier B.V. All rights reserved.