Effect of vagus nerve stimulation on electrical kindling in different stages of seizure severity in freely moving cats

Vagus nerve stimulation (VNS) is an adjunctive therapy for treating pharmacoresistant epilepsy. The present study analyze the effect of VNS on the epileptic activity of amygdala kindling (AK) in different seizure severity stages in freely moving cats. Fourteen adult male cats were used and were stereotaxically implanted in both amygdalae, in thalamic reticular nuclei and in prefrontal cortices. AK was developed by the application of 60 Hz pulse trains that were one second in duration. VNS was applied the following day after the first stages were reached. This stimulation consisted of 10 pulse trains in the one-hour period (1 min on/5 min off) prior to AK. AK stimulation continued until all animals reached stage VI. The behavioral changes induced by VNS were transient and bearable. The animals showed relaxation of the nictitating membrane, ipsilateral anisocoria, swallowing and licking. Intermittent VNS application in stage I induced a delay in AK progression. The effect of VNS on the amygdala afterdischarge duration (AD) did not change progressively. VNS in stages II, III, and IV does not have an inhibitory effect on AK, and the AD further exhibited a progressive development. At the end of the generalized seizures, the animals presented with synchronized bilateral discharges of the spike-wave type (3 Hz) and a behavioral “staring spell”. Our results show that VNS applied during the different stages of seizure severity exerts an anti-epileptogenic effect in stage I but no anti-epileptogenic effect in stages II, III, and IV. These results suggest that VNS applied at stage I of kindling induces a delay of generalized convulsive activity.