Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats

Z. Kovács, K. A. Kékesi, N. Szilágyi, I. Ábrahám, D. Székács, N. Király, E. Papp, I. Császár, É Szego, K. Barabás, H. Péterfy, A. Erdei, T. Bártfai, G. Juhász

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

In normal rats the proinflammatory cytokines like interleukin-1β, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 μg/kg to 350 μg/kg). Repetitive administration of 350 μg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 μg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-d-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.

Original languageEnglish
Pages (from-to)731-742
Number of pages12
JournalNeuroscience
Volume140
Issue number2
DOIs
Publication statusPublished - 2006

Fingerprint

Lipopolysaccharides
Prostaglandins
Cytokines
2-Amino-5-phosphonovalerate
Absence Epilepsy
Prostaglandin Antagonists
Febrile Seizures
Injections
Bicuculline
Kainic Acid
Cyclooxygenase 2
Body Temperature
Interleukin-1
Dinoprostone
Aspartic Acid
Indomethacin
Epilepsy
Interleukin-6
Sleep
Seizures

Keywords

  • epileptic activity
  • indomethacin
  • inflammation
  • lipopolysaccharide

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats. / Kovács, Z.; Kékesi, K. A.; Szilágyi, N.; Ábrahám, I.; Székács, D.; Király, N.; Papp, E.; Császár, I.; Szego, É; Barabás, K.; Péterfy, H.; Erdei, A.; Bártfai, T.; Juhász, G.

In: Neuroscience, Vol. 140, No. 2, 2006, p. 731-742.

Research output: Contribution to journalArticle

Kovács, Z, Kékesi, KA, Szilágyi, N, Ábrahám, I, Székács, D, Király, N, Papp, E, Császár, I, Szego, É, Barabás, K, Péterfy, H, Erdei, A, Bártfai, T & Juhász, G 2006, 'Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats', Neuroscience, vol. 140, no. 2, pp. 731-742. https://doi.org/10.1016/j.neuroscience.2006.02.023
Kovács, Z. ; Kékesi, K. A. ; Szilágyi, N. ; Ábrahám, I. ; Székács, D. ; Király, N. ; Papp, E. ; Császár, I. ; Szego, É ; Barabás, K. ; Péterfy, H. ; Erdei, A. ; Bártfai, T. ; Juhász, G. / Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats. In: Neuroscience. 2006 ; Vol. 140, No. 2. pp. 731-742.
@article{322901d5dc274ab6b8e671d4492da8cf,
title = "Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats",
abstract = "In normal rats the proinflammatory cytokines like interleukin-1β, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 μg/kg to 350 μg/kg). Repetitive administration of 350 μg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 μg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-d-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.",
keywords = "epileptic activity, indomethacin, inflammation, lipopolysaccharide",
author = "Z. Kov{\'a}cs and K{\'e}kesi, {K. A.} and N. Szil{\'a}gyi and I. {\'A}brah{\'a}m and D. Sz{\'e}k{\'a}cs and N. Kir{\'a}ly and E. Papp and I. Cs{\'a}sz{\'a}r and {\'E} Szego and K. Barab{\'a}s and H. P{\'e}terfy and A. Erdei and T. B{\'a}rtfai and G. Juh{\'a}sz",
year = "2006",
doi = "10.1016/j.neuroscience.2006.02.023",
language = "English",
volume = "140",
pages = "731--742",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats

AU - Kovács, Z.

AU - Kékesi, K. A.

AU - Szilágyi, N.

AU - Ábrahám, I.

AU - Székács, D.

AU - Király, N.

AU - Papp, E.

AU - Császár, I.

AU - Szego, É

AU - Barabás, K.

AU - Péterfy, H.

AU - Erdei, A.

AU - Bártfai, T.

AU - Juhász, G.

PY - 2006

Y1 - 2006

N2 - In normal rats the proinflammatory cytokines like interleukin-1β, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 μg/kg to 350 μg/kg). Repetitive administration of 350 μg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 μg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-d-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.

AB - In normal rats the proinflammatory cytokines like interleukin-1β, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 μg/kg to 350 μg/kg). Repetitive administration of 350 μg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 μg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-d-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.

KW - epileptic activity

KW - indomethacin

KW - inflammation

KW - lipopolysaccharide

UR - http://www.scopus.com/inward/record.url?scp=33646510267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646510267&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2006.02.023

DO - 10.1016/j.neuroscience.2006.02.023

M3 - Article

C2 - 16616432

AN - SCOPUS:33646510267

VL - 140

SP - 731

EP - 742

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 2

ER -