Abstract
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 (200μg/kg) and mouse (100μg/kg) pups 2-2.5h 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 Cx3cr1GFP/+ 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.
| Original language | English |
|---|---|
| Article number | e00348 |
| Journal | Brain and Behavior |
| Volume | 5 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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Keywords
- Brain inflammation
- Cytokines
- Febrile seizures
- Lipopolysaccharide
- Microglia
- Temporal lobe epilepsy
ASJC Scopus subject areas
- Behavioral Neuroscience
Cite this
Lipopolysaccharide potentiates hyperthermia-induced seizures. / Eun, Baik-Lin; Abraham, Jayne; Mlsna, Lauren; Kim, Min Jung; Koh, Sookyong.
In: Brain and Behavior, Vol. 5, No. 8, e00348, 01.01.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lipopolysaccharide potentiates hyperthermia-induced seizures
AU - Eun, Baik-Lin
AU - Abraham, Jayne
AU - Mlsna, Lauren
AU - Kim, Min Jung
AU - Koh, Sookyong
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 (200μg/kg) and mouse (100μg/kg) pups 2-2.5h 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 Cx3cr1GFP/+ 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.
AB - 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 (200μg/kg) and mouse (100μg/kg) pups 2-2.5h 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 Cx3cr1GFP/+ 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.
KW - Brain inflammation
KW - Cytokines
KW - Febrile seizures
KW - Lipopolysaccharide
KW - Microglia
KW - Temporal lobe epilepsy
UR - http://www.scopus.com/inward/record.url?scp=84938743013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938743013&partnerID=8YFLogxK
U2 - 10.1002/brb3.348
DO - 10.1002/brb3.348
M3 - Article
C2 - 26357586
AN - SCOPUS:84938743013
VL - 5
JO - Brain and Behavior
JF - Brain and Behavior
SN - 2157-9032
IS - 8
M1 - e00348
ER -