Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: A controlled study

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P_s across the stimulation cycle was measured statistically. P_s was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P_s, unlike LSNS which increased cortical rhythm synchrony and with it, P_s. LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P_s raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.