Lipopolysaccharide‐induced Febrile Convulsions in the Rat: Short‐term Sequelae

Abstract

Summary:Purpose: Febrile convulsions (FCs) occur in children as a result of fever. The mechanisms involved in the genesis of FCs and their long-term consequences on brain development remain unclear. We have developed a model of FC, by using fever as a parameter, to test the hypothesis that fever can lower seizure threshold and to examine the neurologic sequelae of FCs.Methods: Fourteen-day-old rat pups equipped with bodytemperature telemetry devices exhibited ∼1.5• C fevers after lipopolysaccharide (Escherichia coli, 200 µg/kg). During such fevers, concurrently administered doses of kainic acid that are normally subconvulsant were used to induce convulsions with fever. Animals were then killed at varying times for pathological and immunohistochemical studies.Results: The pairing of lipopolysaccharide and subconvulsant kainic acid resulted in convulsions in ∼50% of febrile animals, with very low mortality. To study the neural correlates of these FCs, we used fos immunohistochemistry and found that animals with FCs had fos-positive immunoreactivity in brain regions involved in seizures. After a period of 72 h, we also examined brains for pathologic changes and found no differences among our groups.Conclusions: Our data indicate that a neuroimmune challenge and its accompanying fever reduce the seizure threshold. Furthermore, the FCs induced by fever in this model do not have short-term adverse effects on the brain. In addition, this model, by incorporating physiologic fever, may be useful for examining the role of fever and its constituent mediators in the genesis of FCs. Key Words: LPS-Fever-Febrile convulsions-FosNeonate.Febrile convulsions (FCs) are seizures induced by fever that affect 3 to 5% of children between the ages of 6 months and 5 years and are the most common type of convulsion in humans (1,2). Substantial disagreement exists regarding their effects on the developing brain, both in the acute period and in the months to years after the initial event (3-6). Even the etiology of FCs is unknown. In special cases of FCs, those found in generalized epilepsy with febrile seizures plus (GEFS+), mutations in genes encoding cation channels (specifically sodium channels) as well as the γ -aminobutyric acid receptor (GABAR) have been found to have causal links (7-9). However, GEFS+ is a rare familial disorder with mutations found only in certain pedigrees, and these fail to explain the effect involved in the remaining majority of FCs. Experimental models may elucidate the basic mechanisms involved in these convulsions (10).Many experimental models have used hyperthermiainduced convulsions as a model to study This is because most animals readily convulse when hyperthermic, but not usually when febrile. However, this model may not be appropriate, as fever and hyperthermia are very different physiologic processes (17). Fever is a regulated increase in body temperature that results from an immune challenge. It involves peripheral and central nervous system (CNS) cytokine signaling and generation of prostaglandins t...

Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

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Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

“…Prior to surgery, animals were separated from the dam and placed in a small cage on a heating pad. Anaesthesia was induced using isoflurane (4% induction, 2-2.5% maintenance) and dataloggers were implanted into the abdomen as previously described (Heida et al, 2004). The entire surgical procedure required about 5 min per rat.…”

Ratlarda Endojen ve Eksojen Hiperterminin Sebep Olduğu Nöronal Beyin Hasarı

“…Although there are studies reporting the results based on lipopolysaccharide-induced endogenous hyperthermia (6,8,11), there are limited number of studies investigating the neuronal effects of experimentally-induced exogenous hyperthermia. Our present study uniquely focused on evaluating the [possible] effects of both endogenous and exogenous hyperthermia at 41 °C in rat brain.…”

“…Hyperthermia has been reported to cause apoptosis. In addition, increased apoptotic process continues during hyperthermia (5,6).…”