Abstracts

Lipopolysaccharide potentiates hyperthermia induced seizures: development of a new model of prolonged febrile convulsions

Abstract number : 3.016
Submission category : 1. Translational Research
Year : 2010
Submission ID : 13028
Source : www.aesnet.org
Presentation date : 12/3/2010 12:00:00 AM
Published date : Dec 2, 2010, 06:00 AM

Authors :
Baik-Lin Eun, M. Kim and S. Koh

Rationale: Febrile seizures (FS) are the most prevalent form of early-life seizures, and febrile status epilepticus (FSE) accounts for 25-30% of all childhood SE and over 70% of SE in the first two years of life. While early childhood prolonged febrile convulsions have both acute and long-lasting effects on the developing brain, there is currently no effective therapy. In order to study the role of inflammation and immunity in the development of epilepsy after early-life convulsions, we sought to develop a new febrile convulsion (FCs) model that combines the innate immune activator, lipopolysaccharide (LPS), with hyperthermia-induced seizures to simulate fever from infection. Methods: P14 Long Evans male rats were injected with LPS (200 ug/kg, i.p.) 2.5 h prior to induction of febrile seizures (30 minute exposure to heated air to maintain core temperature between 38-42oC, modified from Dr. Baram s FS model). Latency to seizure onset, threshold temperature, and total number of seizures were quantified. Controls included hyperthermia alone (FS), LPS alone and normothermic littermates. To show electrographic correlates of behavioral seizures, the prefabricated headmounts (Pinnacle) were implanted (3 FS, 3 FCs (LPS FS)). At 0.5, 3 or 24 h after FS or FCs, blood and hippocampal tissue were collected for cytokine assay. Rats underwent exploratory behavior or Barnes maze at P21, and latency to KA-induced seizures was measured at P28. Results: Stable body temperature was maintained in an infant incubator set at 30C until 2.5 h, when slight yet significant rise in temperature was noted in LPS injected pups (36.6 0.1, n=22, vs 37.0 0.1, n=23, p<0.04). FCs (LPS FS) significantly activated IL1-? and TNF-? production in the blood and hippocampus, while hyperthermia seizure (FS) or LPS alone had only modest effects (n=3/group/time). Parallel to an acute increase in cytokine production, LPS primed animals showed a significant decrease in latency to seizure onset (sec) (325.0 16.1, n=22, vs 209.0 17.5, n=23, p<0.001), threshold temperature (41.0 0.2 vs 40.0 0.2, p<0.002), and an increase in total number of seizures (41 2 vs 63 3, p<0.001) compared to FS. EEG confirmed electrographic correlates of seizures manifested by behavioral arrest, hind limb clonus or tonic flexions. The latency to KA-SE at P28 was similarly decreased in animals with prior experience of FS or FCs (83.3 10 (PBS/KA) vs 60.0 5.3 (FS/KA) or 58.4 3.3 (FCs/KA), n=20, p<0.05). No behavioral deficits were noted at 7 days after LPS, FS or FCs.
Translational Research