GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats
GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats
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DOI：
10.1111/j.1460-9568.2007.05533.x
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
van Rijn, Clementina M.
中科院分区：
文献类型：
--
作者：
Bouwman, Brigitte M.;Suffczynski, Piotr;van Rijn, Clementina M.
在这项研究中，氨己烯酸的棘波放电（SWDs）的影响，在WAG/Rij大鼠，失神癫痫的动物模型进行了测量。使用氨己烯酸的目的是增强GABA能神经传递，并以这种方式研究该过程在SWD性质中的作用。该研究在大鼠体内进行，并使用计算模型，以测试可能解释氨己烯酸后SWD变化的不同机制。根据已知的和假定的药物作用机制改变代表GABA水平的模型参数。结果表明，计算模型可以最充分地模拟在体内获得的数据的假设，由于应用氨己烯酸的GABA能神经传递的增强是最明显的丘脑中继核（TC细胞）的水平。此外，氨己烯酸被证明会影响社署的启动和停止机制，反映了危险率。基于这些结果，我们认为TC细胞中的GABA能神经传递积极参与SWD终止。
In this study, the effects of vigabatrin on spike-and-wave discharges (SWDs) were measured in WAG/Rij rats, an animal model of absence epilepsy. Vigabatrin was used with the aim of enhancing GABAergic neurotransmission, and in this way to investigate the role of this process in the properties of SWDs. The study was carried out both in the rat, in vivo, and also using a computational model, in order to test different mechanisms that may account for the changes in SWDs after vigabatrin. The model parameters, representing GABA levels, were changed according to the known, and assumed, mechanism of action of the drug. The results show that the computational model can most adequately simulate the data obtained in vivo on the assumption that the enhancement of GABAergic neurotransmission due to application of vigabatrin is most pronounced at the level of the thalamic relay nuclei (TC cells). Furthermore, vigabatrin was shown to affect both the SWD starting and stopping mechanisms, as reflected by hazard rates. Based on these results, we suggest that GABAergic neurotransmission in TC cells is actively involved in the SWD termination.