Anti-seizure effect and neuronal activity change in the genetic-epileptic model rat with acute and chronic vagus nerve stimulation.
Animals
Brain
/ metabolism
Brain Stem
/ metabolism
Disease Models, Animal
Epilepsy
/ genetics
Male
Neurons
/ metabolism
Proto-Oncogene Proteins c-fos
/ metabolism
Rats
Rats, Wistar
Seizures
/ genetics
Solitary Nucleus
/ metabolism
Thalamus
/ metabolism
Treatment Outcome
Vagus Nerve Stimulation
/ methods
Anti-seizure effect
Neuronal activity change
Noda epileptic rat
Vagus nerve stimulation
Journal
Epilepsy research
ISSN: 1872-6844
Titre abrégé: Epilepsy Res
Pays: Netherlands
ID NLM: 8703089
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
10
03
2019
revised:
14
06
2019
accepted:
24
06
2019
pubmed:
6
7
2019
medline:
27
5
2020
entrez:
6
7
2019
Statut:
ppublish
Résumé
VNS showed time-dependent anti-seizure effect. However, the precise mechanism of VNS in acute and chronic anti-seizure effect has not been fully elucidated. Noda epileptic rat (NER) is genetic epilepsy model rat which exhibits spontaneous generalized tonic-clonic seizure (GTC) approximately once per 30 h and frequent dialeptic seizure (DS). We performed acute and chronic VNS on NER to focus on the acute and chronic anti-epileptic effect and neuronal activity change by VNS. We performed acute VNS (2 h) on 22 NERs (VNS, n = 11, control, n = 11), then subsequently administered chronic (4 weeks) VNS on 10 of 22 NERs (VNS n = 5, control n = 5). We evaluated the acute and chronic anti-seizure effects of VNS on GTC and DS by behavioral and electroencephalographical observation (2 h every week). We carried out double immunofluorescence for biomarkers of short-term (c-Fos) and long-term (ΔFosB) neuronal activation to map regions in the brain that were activated by acute (VNS n = 6, control n = 6) or chronic VNS (VNS n = 5, control n = 5). Furthermore, we performed chronic VNS (4 w) on 12 NERs (VNS n = 6, control n = 6) with long-term observation (8 h a day, 5d per week) to obtain an adequate number of GTCs to elucidate the time dependent anti-epileptic effect on GTC. Acute VNS treatment reduced GTC seizure frequency and total duration of the DS. Chronic VNS resulted in a time-dependent reduction of DS frequency and duration. However, chronic VNS did not show time-dependent reduction of GTC frequency. There were significant c-Fos expressions in the central medial nucleus (CM), mediodorsal thalamic nucleus (MDM), locus coeruleus (LC), and nucleus of solitary tract (NTS) after acute VNS. And there were significant ΔFosB expressions in the lateral septal nucleus (LSV), medial septal nucleus (MSV), MDM, and pontine reticular nucleus caudal (PnC) after chronic VNS. Any decrease in frequency of GTCs by chronic VNS could not be confirmed even with long-term observation. We confirmed acute VNS significantly reduced the frequency of GTC and duration of DS. Chronic VNS decreased the frequency and duration of DS in a time-dependent manner. The brainstem and midline thalamus were activated after acute and chronic VNS. The forebrain was activated only after chronic VNS.
Sections du résumé
BACKGROUND
VNS showed time-dependent anti-seizure effect. However, the precise mechanism of VNS in acute and chronic anti-seizure effect has not been fully elucidated. Noda epileptic rat (NER) is genetic epilepsy model rat which exhibits spontaneous generalized tonic-clonic seizure (GTC) approximately once per 30 h and frequent dialeptic seizure (DS). We performed acute and chronic VNS on NER to focus on the acute and chronic anti-epileptic effect and neuronal activity change by VNS.
METHODS
We performed acute VNS (2 h) on 22 NERs (VNS, n = 11, control, n = 11), then subsequently administered chronic (4 weeks) VNS on 10 of 22 NERs (VNS n = 5, control n = 5). We evaluated the acute and chronic anti-seizure effects of VNS on GTC and DS by behavioral and electroencephalographical observation (2 h every week). We carried out double immunofluorescence for biomarkers of short-term (c-Fos) and long-term (ΔFosB) neuronal activation to map regions in the brain that were activated by acute (VNS n = 6, control n = 6) or chronic VNS (VNS n = 5, control n = 5). Furthermore, we performed chronic VNS (4 w) on 12 NERs (VNS n = 6, control n = 6) with long-term observation (8 h a day, 5d per week) to obtain an adequate number of GTCs to elucidate the time dependent anti-epileptic effect on GTC.
RESULTS
Acute VNS treatment reduced GTC seizure frequency and total duration of the DS. Chronic VNS resulted in a time-dependent reduction of DS frequency and duration. However, chronic VNS did not show time-dependent reduction of GTC frequency. There were significant c-Fos expressions in the central medial nucleus (CM), mediodorsal thalamic nucleus (MDM), locus coeruleus (LC), and nucleus of solitary tract (NTS) after acute VNS. And there were significant ΔFosB expressions in the lateral septal nucleus (LSV), medial septal nucleus (MSV), MDM, and pontine reticular nucleus caudal (PnC) after chronic VNS. Any decrease in frequency of GTCs by chronic VNS could not be confirmed even with long-term observation.
CONCLUSION
We confirmed acute VNS significantly reduced the frequency of GTC and duration of DS. Chronic VNS decreased the frequency and duration of DS in a time-dependent manner. The brainstem and midline thalamus were activated after acute and chronic VNS. The forebrain was activated only after chronic VNS.
Identifiants
pubmed: 31277035
pii: S0920-1211(19)30163-9
doi: 10.1016/j.eplepsyres.2019.106159
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins c-fos
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106159Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.