title: Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: a controlled study.
abstract: 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.
authors.affiliation: Flint Hills Scientific L.L.C., 5020 W15th St. Suite A, Lawrence, KS 66049, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sunderam
authors.forename: I
authors.initials: I
authors.lastname: Osorio
authors.forename: J F
authors.initials: JF
authors.lastname: Watkins
authors.forename: S B
authors.initials: SB
authors.lastname: Wilkinson
authors.forename: M G
authors.initials: MG
authors.lastname: Frei
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
mesh_terms: D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001919:Bradycardia / Q000209:etiology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003344:Cortical Synchronization / Q000187:drug effects / Q000379:methods; D004599:Electric Stimulation Therapy; D008297:Male; D008959:Models, Neurological; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012584:Sciatic Nerve / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D001286:Atropine Derivatives; D010276:Parasympatholytics; C006649:methylatropine