Abstracts

Vagus nerve stimulation (VNS) has been previously shown to be effective for seizure control in some animal models of seizures and in patients with epilepsy. A standardized method for the implantation and the stimulation of the vagus nerve in the rat has not been previously described. Suboptimal seizure control in rats has been attributed to implantation problems. VNS is a highly researched field as a treatment modality for epilepsy and depression. We describe a surgical method of successful VNS implantation and stimulation of the left vagus nerve with EEG recordings. Eleven adult male Sprague Dawley rats weighing 250-400g were used according to a protocol approved by the CCF ARC. Under i.p. ketamine anesthesia (0.1ml/100g), a spiral electrode lead (Cyberonics, Inc., TX, USA) was coiled around the left vagus nerve after isolation from the carotid artery. The 2 spiral contacts measured 5mm in length and 1.5mm in diameter, while the entire lead measured 11.5mm. The 2 spiral electrodes were in a tandem orientation (5mm apart). Using microsurgical tools, the spiral electrodes were carefully wrapped around the left vagus nerve, and a small piece of muscle tissue was sutured around both contacts. The lead was then run subcutaneously to the base of the skull and through an incision in the scalp. The incision in the left side of the neck was sutured. The rats were then placed on a stereotactic frame. For EEG recordings, 5 screw electrodes were implanted in bi-frontal and bi-parietal areas and 2 additional twisted electrodes were implanted in the left and right hippocampal formations. All of the 7 electrodes and the 2 VNS leads were connected to a socket cemented to the skull. EEG recordings were performed using the Vangard digital EEG system. The VNS leads were connected to a NCP model 101 stimulator (Cyberonics, Inc., TX, USA) which was placed over a Cyberonics programming wand. The programming wand was connected to a computer and the stimulations were controlled by Model 250 NCP Programming Software Release. Among the 11 rats that underwent the surgical VNS implantation, only one of them died 5 days after the surgery and prior to any stimulation. The other surgeries were successful, with 8 rats surviving for at least 2 months after surgery. During this period, there was no weight loss and no infection in any of the implanted rats. Left vagus nerve stimulation (on 30 sec, off 5mn, 0.5mA, PW 0.25msec, F 50hz) for periods of 2 hours each was done with concomitant EEG recording with no stimulus artifact recorded on the EEG. These results show that the implantation of left vagus nerve stimulator in conjunction with epidural and intrahippocampal electrodes is safe in the rat. Vagus nerve stimulation using the currently used human paradigms is also safe. This method could be used for the testing of acute and chronic effects of VNS in various rat models of epilepsy and seizures. (Supported by a grant from Cyberonics)