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 experime ntal seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on se izure expression. This study addresses these limitations. The effects of pe riodic left vagus nerve stimulation (LVNS) on chemically-induced seizures i n rats were compared with control groups receiving no stimulation (NoS), le ft sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 13 0 min. Seizures were scored visually and the temporal variation of their pr obability P-s a across the stimulation cycle was measured statistically. P- s was significantly different (P <0.01) for all groups: LSNS had the highes t 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 LV NS nor MA-LVNS induced changes in cortical rhythms ('activation') associate d with decreased P-s unlike LSNS which increased cortical rhythm synchrony and with it. P-s. LVNS alone induced marked bradycardia and moderate hypoxe mia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitat ed seizures, while LVNS both suppressed and facilitated them. The anti-seiz ure effect of LVNS was small and may have, in part, been due to a hemodynam ically-induced deficit in energy substrates. The effects of MA-LVNS on seiz ure duration and P-s raise the possibility that, in the absence of hemodyna mic depression. stimulation of this nerve does not have a strong anti-seizu re effect. (C) 2001 Elsevier Science B.V. All rights reserved.