Abstracts

Rationale: Vagus nerve stimulation (VNS) is a widely used treatment option for patients with refractory partial or generalized epilepsy. The precise mechanism of VNS-induced seizure suppression is still unknown and optimal stimulation parameters remain to be identified. Currently, a reliable animal model to further investigate these VNS-related issues is unavailable. This study evaluates the feasibility of VNS in the alternate day rapid kindling (ADRK-) model, which has been extensively used as a chronic animal model for human refractory partial epilepsy, and more specifically temporal lobe epilepsy (TLE).Methods: Wistar rats (n=5) were implanted with a custom made self-sizing spiral silicone cuff-electrode around the vagus nerve and stimulation/recording depth electrodes were placed in both hippocampi following ketamine/xylazine anesthesia. After recovery, the ADRK-protocol was initiated in the right hippocampus. When the rats were fully kindled, acute VNS (0.75mA, 30Hz, 500µs, 60s) was applied together with the kindling stimulus (retesting paradigm of the ADRK-protocol). Subsequently, long-term VNS (0.75mA, 30Hz, 500µs, 30s/5min during 2 weeks) was performed during retesting the fully kindled status of the rats.Results: The rats recovered well from surgery. Left VNS was well tolerated by all animals. Acute VNS seems to have no effect on stage 5 seizures, whereas long-term VNS affects seizure severity in the ADRK-model by reducing stage 5 seizures to stage 4 seizures.Conclusions: Implantation of a vagus nerve cuff electrode combined with hippocampal depth electrodes is feasible and safe in the rat, as well as applying acute or long-term VNS using stimulation parameters analogous to those used in the clinic in fully kindled rats. The long-term efficacy of VNS should be further explored in the ADRK-model.