Abstracts

Rationale: In a longitudinal animal study, we investigated the effect of Vagus Nerve Stimulation (VNS) on seizure burden employing the lithium-pilocarpine model of epilepsy in rats. We tested the hypothesis that the seizure burden is reduced upon stimulation of the vagus nerve over a comparatively long time. This hypothesis was tested by utilizing a protocol with VNS alternatively ON and OFF for 2 weeks at a time. The plasticity of the effect of VNS on seizure burden also was investigated. Methods: Three male Sprague-Dawley rats were induced to chronic epilepsy according to the lithium-pilocarpine model of epilepsy [1]. Rats were subsequently implanted with a total of 8 Tungsten microwires for long-term EEG recording from thalamus, hippocampus and cortex, and with two leads (Cyberonics Inc., Houston, TX) wrapped around the left vagus nerve in the ventral cervical region for electrical stimulation by externally positioned, programmable, stimulators (A-M Systems Inc., Sequim, WA). The VNS was delivered periodically (60 sec ON, 300 sec OFF). During the ON phase, a 30 Hz train of pulses, each of 220 μsec in duration and 0.5 mA in amplitude, was delivered. The long-term EEG was recorded and analyzed over five separate periods of the experiment that each lasted for at least 2 weeks: Baseline 1 (no stimulation), Stimulation 1 (VNS stimulation), Baseline 2 (no stimulation), Stimulation 2 (VNS stimulation), Baseline 3 (no stimulation). Seizures' occurrence and duration were detected by retrospective analysis of the continuously recorded EEG via in-house developed software based on Teager energy. Seizure burden was defined as the percentage of recording time a rat spent in ictal state. Results: All three rats showed a statistically significant (p<0.05, t-test) reduction of seizure burden during VNS stimulation periods when compared with their preceding baselines (e.g. see Figure 1). In addition, a trend towards reduction of seizure burden over time (from Baseline 1 to Baseline 3) was observed in two rats. In the third rat, increase of the seizure burden was observed from Baseline 1 to 2, and saturation from Baseline 2 to 3. Conclusions: VNS was found to be effective in significantly reducing the seizure burden in the limited number of rats with chronic epilepsy that participated in this longitudinal study. Furthermore, plasticity of the VNS effect was observed in the majority of the rats. These results provide supporting evidence for the longitudinal use of VNS in reducing seizure burden. Acknowledgement: This study was funded by Cyberonics Inc., Houston, TX. [1] Persinger, M.A., K. Makarec, and J.-C. Bradley, "Characteristics of limbic seizures evoked by peripheral injections of lithium and pilocarpine". Physiology & Behavior. 44(1) (1988) 27-37.