Abstracts

Rationale: Vagus nerve stimulation (VNS) Therapy is an FDA-approved treatment for medically refractory partial epilepsy that is widely used clinically. Determining if VNS elevates seizure threshold in an animal model of partial epilepsy remains to be established. Here, we asked whether VNS would elevate the threshold for evoking limbic seizures in the kindling model in rats. Methods: Male Sprague-Dawley rats underwent stereotaxic implantation of a bipolar electrode in the right amydala and a stimulating electrode surrounding the left vagal nerve. Following induction of kindling, the current intensity required to evoke electrographic seizures was examined every 2-3 days until identical thresholds were found on three consecutive trials. VNS was then turned on in the treatment groups, and seizure threshold was tested after 60 min and again after 1 week. Dummy-treated control animals underwent the same surgical and kindling procedures, but VNS devices were not activated. We tested the effectiveness of the standard VNS protocol used clinically as well as an experimental protocol, termed microburst . Results: Similar to previous findings of seizure threshold declining over time in kindled animals, seizure threshold significantly decreased from baseline to the 60-min (p<0.05) and 1-week (p<0.05) thresholds in dummy-treated controls (n=11 animals). By contrast, standard VNS (0.5 mA, n=5 animals) prevented the reduction of seizure threshold from baseline when tested at both 60 min and 1 week (p>0.05 for each timepoint, n=5 animals). Similarly, microburst VNS (0.5 mA; n=4 animals) prevented the reduction of seizure threshold at both 60 min and 1 week (p>0.05 for each time point and each treatment intensity). Conclusions: These findings demonstrate that VNS Therapy is an effective anticonvulsant treatment in the kindling model, and this model can be used for systematic modification and optimization of VNS parameters as well as elucidation of the cellular mechanisms underlying efficacy of VNS. Supported by a grant from Cyberonics, Inc.