Dedeurwaerdere S, Gilby K, Vonck K, Delbeke J, Boon P, McIntyre D
Laboratory for Clinical and Experimental Neurophysiology and Reference Centre for Refractory Epilepsy, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Neuroscience. 2006 Jul 21;140(4):1443-51. doi: 10.1016/j.neuroscience.2006.03.014. Epub 2006 May 2.
Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy. Using a seizure-prone Fast-kindling rat strain with known comorbid behavioral features, we investigated the effects of VNS on spatial memory, epileptogenesis, kindled seizures and body weight. Electrodes were implanted in both amygdalae and around the left vagus nerve of 17 rats. Following recovery, rats were tested in the Morris water-maze utilizing a fixed platform paradigm. The VNS group received 2 h of stimulation prior to entering the Morris water-maze. Rats were then tested in the kindling paradigm wherein the VNS group received 2 h of stimulation prior to daily kindling stimulation. Finally, the abortive effects of acute VNS against kindling-induced seizures were determined in fully kindled rats by applying VNS immediately after the kindling pulse. Body weight, water consumption and food intake were measured throughout. Memory performance in the Morris water-maze was not different between control and vagus nerve stimulation rats. Similarly, kindling rate was unaffected by antecedent VNS. However, pro-convulsive effects (P<0.05) were noted, when VNS was administered prior to the kindling pulse in fully kindled rats. Yet, paradoxically, VNS showed anti-convulsant effects (P<0.01) in those rats when applied immediately after the kindling stimulus. Body weight was significantly lower throughout kindling (P<0.01) in VNS-treated rats compared with controls, which was associated with reduced food intake (P<0.05), but without difference in water consumption. VNS appears to be devoid of significant cognitive side effects in the Morris water-maze in Fast rats. Although VNS exhibited no prophylactic effect on epileptogenesis or seizure severity when applied prior to the kindling stimulus, it showed significant anti-convulsant effects in fully kindled rats when applied after seizure initiation. Lastly, VNS prevented the weight gain associated with kindling through reduced food intake.
迷走神经刺激（VNS）是难治性癫痫的一种辅助治疗方法。我们使用具有已知共病行为特征的易癫痫快速点燃大鼠品系，研究了VNS对空间记忆、癫痫发生、点燃性癫痫发作和体重的影响。将电极植入17只大鼠的双侧杏仁核和左迷走神经周围。恢复后，利用固定平台范式在莫里斯水迷宫中对大鼠进行测试。VNS组在进入莫里斯水迷宫之前接受2小时的刺激。然后在点燃范式中对大鼠进行测试，其中VNS组在每日点燃刺激之前接受2小时的刺激。最后，在完全点燃的大鼠中，通过在点燃脉冲后立即应用VNS来确定急性VNS对点燃性癫痫发作的中止作用。全程测量体重、饮水量和食物摄入量。对照组和迷走神经刺激组大鼠在莫里斯水迷宫中的记忆表现没有差异。同样，先前的VNS对点燃率没有影响。然而，在完全点燃的大鼠中，在点燃脉冲之前给予VNS时，观察到促惊厥作用（P<0.05）。然而，自相矛盾的是，在点燃刺激后立即应用VNS时，VNS在这些大鼠中显示出抗惊厥作用（P<0.01）。与对照组相比，VNS治疗组大鼠在整个点燃过程中的体重显著降低（P<0.01），这与食物摄入量减少（P<0.05）有关，但饮水量没有差异。在快速大鼠的莫里斯水迷宫中，VNS似乎没有明显的认知副作用。虽然在点燃刺激之前应用VNS对癫痫发生或癫痫发作严重程度没有预防作用，但在癫痫发作开始后应用时，VNS在完全点燃的大鼠中显示出显著的抗惊厥作用。最后，VNS通过减少食物摄入量防止了与点燃相关的体重增加。
