Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

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Abstract
Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect. VNS (1 mA, 30 Hz, 500 microseconds pulse width) was administered continuously for 0.1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals. The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min. The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.