Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem

K. Rijkers; H. J.M. Majoie; M. W. Aalbers; M. Philippens; V. M. Doenni; J. S.H. Vles; H. M.W. Steinbusch; V. M.P. Moers-Hornikx; D. A. Hopkins; G. Hoogland

doi:10.1016/j.jchemneu.2012.09.004

Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem

K. Rijkers, H. J.M. Majoie, M. W. Aalbers, M. Philippens, V. M. Doenni, J. S.H. Vles, H. M.W. Steinbusch, V. M.P. Moers-Hornikx, D. A. Hopkins, G. Hoogland

Medicine

Medicine

Résultat de recherche: Article › examen par les pairs

1 Citation (Scopus)

Résumé

Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC).Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1. min prior to the kindling stimulus and lasting for 2. min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48. h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B.VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm² were significantly more frequent in the left DMV than in the right (χ²(1)=26.2, p<0.01), independent of whether the vagus nerve was stimulated.We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.

Langue d'origine	English
Pages (de-à)	1-9
Nombre de pages	9
Journal	Journal of Chemical Neuroanatomy
Volume	46
Numéro de publication	1-2
DOI	https://doi.org/10.1016/j.jchemneu.2012.09.004
Statut de publication	Published - déc. 2012

Note bibliographique

Funding Information:
The authors would like to thank Prof. T.E. Dinan for the use of the WPI Accupulser and Stimulus Isolation Unit, Dr. V. van Kranen-Mastenbroek for the use of the Vangard EEG system, Mr. K. Mullet, Mr. P. van Venrooij and Mr. V. Duysens (Medtronic Bakken Research Center) for providing us with VNS electrodes, and Drs. M.A.M. Lemmens for her help with analysis of the nNOS staining. Dr. K. Rijkers was supported by grant #92003453 from the Dutch Scientific Organization . Dr. D.A. Hopkins was supported by an International Stichting Alzheimer Onderzoek (ISAO) Visiting Professorship.

ASJC Scopus Subject Areas

Cellular and Molecular Neuroscience

Accès au document

10.1016/j.jchemneu.2012.09.004

Autres fichiers et liens

Citer

Rijkers, K., Majoie, H. J. M., Aalbers, M. W., Philippens, M., Doenni, V. M., Vles, J. S. H., Steinbusch, H. M. W., Moers-Hornikx, V. M. P., Hopkins, D. A., & Hoogland, G. (2012). Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem. Journal of Chemical Neuroanatomy, 46(1-2), 1-9. https://doi.org/10.1016/j.jchemneu.2012.09.004

@article{f336d2c8ffe54281abf8d3fcef5f2ce2,

title = "Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem",

abstract = "Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC).Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1. min prior to the kindling stimulus and lasting for 2. min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48. h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B.VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm2 were significantly more frequent in the left DMV than in the right (χ2(1)=26.2, p<0.01), independent of whether the vagus nerve was stimulated.We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.",

author = "K. Rijkers and Majoie, {H. J.M.} and Aalbers, {M. W.} and M. Philippens and Doenni, {V. M.} and Vles, {J. S.H.} and Steinbusch, {H. M.W.} and Moers-Hornikx, {V. M.P.} and Hopkins, {D. A.} and G. Hoogland",

note = "Funding Information: The authors would like to thank Prof. T.E. Dinan for the use of the WPI Accupulser and Stimulus Isolation Unit, Dr. V. van Kranen-Mastenbroek for the use of the Vangard EEG system, Mr. K. Mullet, Mr. P. van Venrooij and Mr. V. Duysens (Medtronic Bakken Research Center) for providing us with VNS electrodes, and Drs. M.A.M. Lemmens for her help with analysis of the nNOS staining. Dr. K. Rijkers was supported by grant #92003453 from the Dutch Scientific Organization . Dr. D.A. Hopkins was supported by an International Stichting Alzheimer Onderzoek (ISAO) Visiting Professorship.",

year = "2012",

month = dec,

doi = "10.1016/j.jchemneu.2012.09.004",

language = "English",

volume = "46",

pages = "1--9",

journal = "Journal of Chemical Neuroanatomy",

issn = "0891-0618",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - Rat vagus nerve stimulation model of seizure suppression

T2 - nNOS and ΔFos B changes in the brainstem

AU - Rijkers, K.

AU - Majoie, H. J.M.

AU - Aalbers, M. W.

AU - Philippens, M.

AU - Doenni, V. M.

AU - Vles, J. S.H.

AU - Steinbusch, H. M.W.

AU - Moers-Hornikx, V. M.P.

AU - Hopkins, D. A.

AU - Hoogland, G.

N1 - Funding Information: The authors would like to thank Prof. T.E. Dinan for the use of the WPI Accupulser and Stimulus Isolation Unit, Dr. V. van Kranen-Mastenbroek for the use of the Vangard EEG system, Mr. K. Mullet, Mr. P. van Venrooij and Mr. V. Duysens (Medtronic Bakken Research Center) for providing us with VNS electrodes, and Drs. M.A.M. Lemmens for her help with analysis of the nNOS staining. Dr. K. Rijkers was supported by grant #92003453 from the Dutch Scientific Organization . Dr. D.A. Hopkins was supported by an International Stichting Alzheimer Onderzoek (ISAO) Visiting Professorship.

PY - 2012/12

Y1 - 2012/12

N2 - Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC).Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1. min prior to the kindling stimulus and lasting for 2. min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48. h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B.VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm2 were significantly more frequent in the left DMV than in the right (χ2(1)=26.2, p<0.01), independent of whether the vagus nerve was stimulated.We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.

AB - Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC).Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1. min prior to the kindling stimulus and lasting for 2. min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48. h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B.VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm2 were significantly more frequent in the left DMV than in the right (χ2(1)=26.2, p<0.01), independent of whether the vagus nerve was stimulated.We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.

UR - http://www.scopus.com/inward/record.url?scp=84870671719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870671719&partnerID=8YFLogxK

U2 - 10.1016/j.jchemneu.2012.09.004

DO - 10.1016/j.jchemneu.2012.09.004

M3 - Article

C2 - 23022956

AN - SCOPUS:84870671719

SN - 0891-0618

VL - 46

SP - 1

EP - 9

JO - Journal of Chemical Neuroanatomy

JF - Journal of Chemical Neuroanatomy

IS - 1-2

ER -

Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem

Résumé

Note bibliographique

ASJC Scopus Subject Areas

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer