Acute seizure-suppressing effect of vagus nerve stimulation in the amygdala kindled rat

Purpose: Vagus nerve stimulation (VNS) is a moderately effective anti-epileptic treatment. Clinically relevant animal models that are suitable to study the mechanism of action of VNS are not available. The aim of the current study was to develop a clinically relevant animal model for VNS-treated epilepsy that can be used to study the mechanism of action of VNS. Methods: The anticonvulsive effect of VNS was studied in fully kindled rats by measuring behavioral and electrophysiological parameters. Afferent vagus nerve activation was confirmed by quantifying nNOS immunoreactive cells in the nucleus of the solitary tract (NTS). Results: VNS rats had more nNOS immunoreactive cells/mm(2) in the NTS than shams. VNS induced a >25% decrease in stage 5 duration (S5D) in 32% of rats. Prior to VNS this type of responders suffered from seizures with a longer total seizure duration (TSD) than non-responders. In 21% of rats VNS resulted in a >25% decrease in TSD. This type of responders had a shorter TSD prior to VNS than non-responders. In 29% of rats VNS resulted in >200% increase in stage 5 latency (S5L). This type of responders had higher kindling rates than non-responders. Conclusion: The VNS-treated kindled rat is a clinically relevant animal model because it is a chronic epilepsy model that responds to VNS with effects that are comparable to the effects of VNS in epilepsy patients. In addition, this study demonstrates that VNS-treated kindled rats can be used to study the mode of action of VNS using immunohistochemical techniques.