Vagus nerve stimulation elevates seizure threshold in the kindling model
Vagus nerve stimulation elevates seizure threshold in the kindling model
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DOI：
10.1111/j.1528-1167.2012.03646.x
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发表时间：
2012-11-01
期刊：
影响因子：
5.6
通讯作者：
McNamara, James O.
中科院分区：
文献类型：
--
作者：
Alexander, Georgia M.;McNamara, James O.
目的：迷走神经刺激 (VNS) 可以部分缓解部分患者的难治性部分性癫痫发作。最佳的刺激模式和抗癫痫作用的机制尚不确定。在癫痫动物模型中建立 VNS 的功效将为解决这些问题提供实验准备。我们试图确定 VNS 是否在癫痫点燃模型中发挥抗癫痫作用。方法：我们在成年大鼠的右侧杏仁核中植入双极刺激电极，并在左侧迷走神经周围植入 VNS 装置。诱导点燃后，通过量化诱发癫痫发作所需的杏仁核电极电流来确定电图癫痫阈值（EST）。一旦建立了稳定的 EST，VNS 设备就会被编程为提供美国食品和药物管理局 (FDA) 批准的临床使用（标准）或实验（微爆发）模式的可变强度刺激。 VNS 装置在对照动物中的编程相同，只是不传递电流。在对照组和迷走神经刺激组中分别在 60 分钟和 1 周时检查 EST。主要发现：在设备编程后 60 分钟和 1 周进行测试时，在对照动物中检测到 EST 值显着降低。在设备编程后 60 分钟或 1 周进行测试时，临床使用和实验模式的 VNS 均阻止了对照动物明显 EST 的减少。意义：这些发现建立了一种实验准备，可用于阐明 VNS 的抗癫痫机制，并确定在提高癫痫阈值方面最有效的 VNS 模式。
Purpose: Vagus nerve stimulation (VNS) provides partial relief of medically refractory partial seizures in a subset of patients. The optimal pattern of stimulation and the mechanism of the antiseizure effects are uncertain. Establishing the efficacy of VNS in an animal model of epilepsy would provide an experimental preparation with which to address these questions. We sought to determine whether VNS exerted antiseizure effects in the kindling model of epilepsy.Methods: We implanted adult rats with bipolar stimulating electrodes in the right amygdala and VNS devices around the left vagus nerve. Following induction of kindling, electrographic seizure threshold (EST) was determined by quantifying the amygdala electrode current required to evoke a seizure. Once stable ESTs were established, VNS devices were programmed to deliver U.S. Food and Drug Administration (FDA)approved, clinically used (standard) or an experimental (microburst) pattern of stimulation of variable intensity. VNS devices were programmed identically in control animals except that no current was delivered. EST was examined at 60 min and 1 week in the control and vagus nerve stimulated groups.Key Findings: Significant reductions of EST values were detected in control animals when tested both 60 min and 1 week following device programming. Both clinically used and experimental patterns of VNS prevented the reduction of EST evident in control animals when tested either 60 min or 1 week after device programming.Significance: These findings establish an experimental preparation with which to elucidate the antiseizure mechanisms of VNS and to determine patterns of VNS most effective at elevating seizure threshold.