Cargando…
Lipopolysaccharide potentiates hyperthermia-induced seizures
BACKGROUND: Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559014/ https://www.ncbi.nlm.nih.gov/pubmed/26357586 http://dx.doi.org/10.1002/brb3.348 |
_version_ | 1782388704344539136 |
---|---|
author | Eun, Baik-Lin Abraham, Jayne Mlsna, Lauren Kim, Min Jung Koh, Sookyong |
author_facet | Eun, Baik-Lin Abraham, Jayne Mlsna, Lauren Kim, Min Jung Koh, Sookyong |
author_sort | Eun, Baik-Lin |
collection | PubMed |
description | BACKGROUND: Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. METHODS: The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2–2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice. RESULTS: Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. CONCLUSIONS: Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS. |
format | Online Article Text |
id | pubmed-4559014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45590142015-09-09 Lipopolysaccharide potentiates hyperthermia-induced seizures Eun, Baik-Lin Abraham, Jayne Mlsna, Lauren Kim, Min Jung Koh, Sookyong Brain Behav Original Research BACKGROUND: Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. METHODS: The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2–2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice. RESULTS: Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. CONCLUSIONS: Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS. John Wiley & Sons, Ltd 2015-08 2015-06-02 /pmc/articles/PMC4559014/ /pubmed/26357586 http://dx.doi.org/10.1002/brb3.348 Text en © 2015 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Eun, Baik-Lin Abraham, Jayne Mlsna, Lauren Kim, Min Jung Koh, Sookyong Lipopolysaccharide potentiates hyperthermia-induced seizures |
title | Lipopolysaccharide potentiates hyperthermia-induced seizures |
title_full | Lipopolysaccharide potentiates hyperthermia-induced seizures |
title_fullStr | Lipopolysaccharide potentiates hyperthermia-induced seizures |
title_full_unstemmed | Lipopolysaccharide potentiates hyperthermia-induced seizures |
title_short | Lipopolysaccharide potentiates hyperthermia-induced seizures |
title_sort | lipopolysaccharide potentiates hyperthermia-induced seizures |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559014/ https://www.ncbi.nlm.nih.gov/pubmed/26357586 http://dx.doi.org/10.1002/brb3.348 |
work_keys_str_mv | AT eunbaiklin lipopolysaccharidepotentiateshyperthermiainducedseizures AT abrahamjayne lipopolysaccharidepotentiateshyperthermiainducedseizures AT mlsnalauren lipopolysaccharidepotentiateshyperthermiainducedseizures AT kimminjung lipopolysaccharidepotentiateshyperthermiainducedseizures AT kohsookyong lipopolysaccharidepotentiateshyperthermiainducedseizures |