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

Sridhar Sunderam, Ivan Osorio, James F. Watkins, Steven B. Wilkinson, Mark G. Frei, Richard E. Davis

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 Ps across the stimulation cycle was measured statistically. Ps 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 Ps, unlike LSNS which increased cortical rhythm synchrony and with it, Ps. 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 Ps raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.

Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalBrain Research
Issue number1-2
StatePublished - Nov 9 2001

Bibliographical note

Funding Information:
Presented in part at the Annual Meeting of the American Epilepsy Society, San Diego, 1998. The authors thank Joe La Manna, Ph.D, Michelle Puchowicz, Ph.D, and Anthony Paolo, Ph.D., for their useful comments. This research was supported in part by the Doris Flynn and Hoescht-Marion-Roussel Awards to Ivan Osorio, and by NIH grant #5R44NS34630-03.


  • 3-Mercaptoprionic acid
  • Anti-seizure effect
  • Convulsant
  • Left vagus nerve stimulation
  • Seizure probability

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


Dive into the research topics of 'Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: A controlled study'. Together they form a unique fingerprint.

Cite this