Cell swelling precedes seizures induced by inhibition of astrocytic metabolism
Cell swelling precedes seizures induced by inhibition of astrocytic metabolism
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DOI：
10.1016/j.eplepsyres.2008.03.012
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发表时间：
2008-08-01
影响因子：
2.2
通讯作者：
Willoughby, John O.
中科院分区：
文献类型：
--
作者：
Broberg, Marita;Pope, Kenneth J.;Willoughby, John O.
目前尚不清楚在癫痫发作起始期间非发作和发作活动之间的界面发生了什么过程，在这项研究中，使用麻痹清醒大鼠，我们用氟柠檬酸（FC）局部抑制星形胶质细胞代谢，引起癫痫发作。我们测量了发作发作期间脑电图（EEG）（0-300 Hz）和细胞外离子浓度的变化，确定了与阻抗确定的细胞肿胀的可能关系。在显示发作活动的动物（69%）中，有棘波放电，棘波放电后有扩散性抑制和扩散性抑制，但没有任何放电。在高比例的棘波放电（>95%）中，就在第一次棘波放电之前，细胞外间隙的体积减少。在细胞肿胀开始后和放电前，高频（150-300 Hz）EEG活动增加，细胞外钾离子浓度增加，细胞外钙离子浓度减少，我们认为EEG和离子变化不是细胞肿胀的原因。由于注射部位星形胶质细胞的代谢失败导致的细胞肿胀可能会释放兴奋性氨基酸。与此同时，我们的研究结果表明，离子稳态没有得到维持，神经元的兴奋性和同步性增加。这些可能是将正常大脑活动转变为发作活动的驱动因素。皇冠版权所有（C）2008年出版的爱思唯尔B. V.保留所有权利。
It is currently unknown what processes take place at the interface between non-ictal and ictal activity during seizure initiation.In this study, using paralysed awake rats, we focally inhibited astrocytic metabolism with fluorocitrate (FC), causing seizures. We measured changes in electroencephalogram (EEG) (0-300 Hz), and extracellular ion-concentrations during ictal onsets defining possible relationships with impedance-determined cell swelling.In animals showing ictal activity (69%) there were spike-wave discharges, spike-wave discharges followed by spreading depression and spreading depression without any discharges. In a high proportion of spike-wave discharges (>95%), just prior to the first spike-wave discharge, there was a decrease in the volume of the extracellular space. Following the initiation of cell swelling and prior to discharges, there were increases in high-frequency (150-300 Hz) EEG activity, increases in extracellular potassium- and decreases in extracellular calcium-concentrations.We suggest that EEG and ionic changes are not causative of cell swelling. Cell swelling due to metabolic failure in astrocytes at the injected site may release excitatory amino acids. At the same time, our results suggest ion homeostasis is not maintained and increased neuronal excitability and synchronisation occur. These could be the drivers changing normal brain activity into ictal activity. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.