Abstracts

Rationale: Vagus nerve stimulation (VNS) has been shown to be an effective means of treating epilepsy in humans. Surprisingly, efficacy of chronic VNS has not been studied in rat models of chronic epilepsy. We determined efficacy of VNS, using standard clinical stimulation parameters, in order to validate a model with which to study the effect of systematic variations of VNS parameters. Methods: Adult male Sprague-Dawley rats (N=33) from Harlan Laboratories were divided into 3 groups. Status epilepticus (SE) was induced in Group A (N=22) by means of 3 mmol/kg intraperitoneal (IP) lithium chloride followed 24 hrs later by 30 mg/kg pilocarpine subcutaneously. SE was allowed to progress until spontaneous cessation 18-24 hrs later. Group B (N=5) was pretreated with diazepam (10mg/kg IP) and phenobarbital (25mg/kg IP) 10 minutes prior to induction of SE in order to prevent SE. Group C (N=6) served as naïve controls. Six weeks post SE, all animals were implanted with 4 stainless steel epidural electrodes, and allowed 1 week recovery. EEG was then continuously recorded over a 4 week period, in order to establish a baseline seizure frequency. A model 309 VNS device was then implanted subcutaneously behind the shoulders and connected to an electrode attached to the left vagus nerve. Rats were allowed a 2 week recovery period before the VNS device was turned on and chronic monitoring begun. VNS settings were: output current 0.5 mA, pulse width 250 μsec, frequency 30 Hz, 30 sec on, 5 min off. Statistical significance was determined using a paired T-test. Results: Mean seizure frequency for the 4 week baseline recording was 114 ± 40 (range 75 to 164)/week. Preliminary data from weeks 1 and 2 of the VNS stimulation period were used for the initial analysis. Mean seizure frequency during the first week of 12 weeks of recording after onset of VNS was 80 ± 54 (range 2 to 160)/week (p< 0.2). For the 2nd week, mean seizure frequency was 65 ± 37 (range 13 to 124)/week (p< 0.009). Data collection is continuing and results of the entire VNS stimulation period will be presented.