Elsevier

Epilepsy Research

Volume 22, Issue 1, September 1995, Pages 53-62
Epilepsy Research

Regional induction of fos immunoreactivity in the brain by anticonvulsant stimulation of the vagus nerve

https://doi.org/10.1016/0920-1211(95)00035-9Get rights and content

Abstract

Electrical stimulation of the vagus nerve exerts an antiepileptic effect on human partial-onset epilepsy, but little is known about the brain structures that mediate this phenomenon. Fos is a nuclear protein that is expressed under conditions of high neuronal activity. We utilized fos immunolabeling techniques on Sprague-Dawley rat brains to identify regions that are activated by antiepileptic stimulation of the left vagus nerve. Vagus nerve stimulation (VNS) induced specific nuclear fos immunolabeling in several forebrain structures, including the posterior cortical amygdaloid nucleus, cingulate and retrosplenial cortex, ventromedial and arcuate hypothalamic nuclei. In the brainstem, there was specific immunolabeling in vagus nerve nuclei, in the A5 and locus ceruleus noradrenergic nuclei, and in the cochlear nucleus. No labeling of these structures occurred in sham-operated, unstimulated control animals. Intense labeling also occurred in habenular nucleus of thalamus after vagus nerve stimulation, whereas only mild staining occurred in unstimulated animals. Several of the brain structures activated by VNS are important for genesis or regulation of seizures in the forebrain. These structures may mediate the antiepileptic effect of VNS.

References (64)

  • E.J. Hammond et al.

    Neurochemical effects of vagus nerve stimulation in humans

    Brain Res.

    (1992)
  • D.G. Herrera et al.

    N-methyl-d-aspartate receptors mediate activation of the c-fos proto-oncogene in a model of brain injury

    Neuroscience

    (1990)
  • P. Hughes et al.

    Muscarinic receptor-mediated induction of Fos protein in rat brain

    Neurosci. Lett.

    (1993)
  • P. Levitt et al.

    Central adrenergic receptor changes in the inherited noradrenergic hyperinnervated mutant mouse tottering

    Brain Res.

    (1987)
  • W. Maixner

    Vagal modulation of nociception: A critique

    APS J.

    (1992)
  • J.W. Miller et al.

    Characterization of GABAergic seizure regulation in the midline thalamus

    Neuropharmacology

    (1990)
  • S. Mondragon et al.

    Suppression of motor seizures after specific thalamotomy in chronic epileptic monkeys

    Epilepsy Res.

    (1990)
  • T.H. Murphy et al.

    L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes

    Neuron

    (1991)
  • J.A. Noebels et al.

    Altered hippocampal network excitability in the hypernoradrenergic mutant mouse tottering

    Brain Res.

    (1990)
  • J.A. Ricardo et al.

    Anatomic evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat

    Brain Res.

    (1978)
  • C.B. Saper et al.

    Efferent connections of the parabrachial nucleus in the rat

    Brain Res.

    (1980)
  • A. Zanchetti et al.

    The effects of vagal afferent stimulation on the EEG pattern of the cat

    EEG Clin. Neurophysiol.

    (1952)
  • E. Ben-Menachem et al.

    Vagus nerve stimulation for treatment of partial seizures. I. A controlled study of effect on seizures

    Epilepsia

    (1994)
  • J.-L. Daval et al.

    Mouse brain c-fos mRNA distribution following a single electroconvulsive shock

    J. Neurochem.

    (1989)
  • P. DeTogni et al.

    Detection of fos protein during osteogenesis by monoclonal antibodies

    Mol. Cell Biol.

    (1988)
  • C.L. Faingold et al.

    Neuronal networks in convulsant drug-induced seizures

  • G.H. Fromm et al.

    How does vagal nerve stimulation prevent seizures?

    Epilepsia

    (1993)
  • R.L. Gellman et al.

    Pyramidal cells in pyriform cortex receive a convergence of inputs from monoamine activated GABAergic interneurons

    Brain Res.

    (1993)
  • R.L. Gellman et al.

    Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development

    J. Pharmacol. Exp. Ther.

    (1987)
  • R. George et al.

    Vagus nerve stimulation for treatment of partial seizures. 3. Long-term follow-up on first 67 patients exiting a controlled study

    Epilepsia

    (1994)
  • M.S. Goldman et al.

    Symptomatic and functional outcome of stereotactic ventralis lateralis thalamotomy for intention tremor

    J. Neurosurg.

    (1992)
  • Gowers, W.R., Epilepsy and Other Chronic Convulsive Diseases, J. and A. Churchill, London, pp....
  • Cited by (261)

    • Vagal Nerve Stimulation: A Bibliometric Analysis of Current Research Trends

      2023, Neuromodulation
      Citation Excerpt :

      VNS modulates neural circuitry and promotes cortical plasticity by stimulating vagal afferent fibers, thereby modulating the activity of neuronal pathways and levels of neurotransmitters downstream.17 In particular, VNS has been shown to increase locus coeruleus (LC) activity,18–20 and to stimulate the release of norepinephrine (NE) in the neuropil of the amygdala,21 hippocampus,22,23 and the prefrontal cortex.23,24 NE elevation has been shown to have anticonvulsant properties, which may partially explain how VNS works to reduce seizure frequency.25–27

    • Vagus nerve stimulation

      2023, Neurostimulation for Epilepsy: Advances, Applications and Opportunities
    View all citing articles on Scopus
    View full text