Maturation of kainic acid seizure-brain damage syndrome in the rat. II. Histopathological sequelae

Nitecka, L; Tremblay, E.; Charton, Gérard; Bouillot, J.P.; Berger, Michael L.; Ben‐Ari, Yehezkel

doi:10.1016/0306-4522(84)90289-6

Cited by 343 publications

(205 citation statements)

References 53 publications

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“…This finding is replicated in studies that use hyperthermia as a model for FCs (63) as well as in humans (6). This, however, is not solely a property of FCs, as some studies show that infant rats are resistant to the deleterious effects of the same types of seizures that in adult rats cause significant neuronal cell death and gliosis throughout the brain (58,(64)(65)(66). Thus despite an increased excitability of the immature brain, it has remarkable resistance to cell death, most likely due to large synaptic spaces and an increased ability to buffer intracellular calcium (67).…”

Section: Discussionmentioning

confidence: 75%

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

2004

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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...

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Section: Discussionmentioning

confidence: 75%

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

2004

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“…The oral automatisms at the onset of seizures, which generally signify a limbic origin [15,27], suggested that EEGs should be recorded from the amygdala and hippocampus. Indeed, EEG confirmation of behavioral seizures was demonstrated in rats implanted with multiple bipolar electrodes aimed at these structures.…”

Section: The Eeg Features Of Hyperthermic Seizures In the Infant Ratmentioning

confidence: 99%

Febrile seizures: an appropriate-aged model suitable for long-term studies

Baram

Gerth

Schultz

1997

Developmental Brain Research

233

242

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Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as neuronal loss and temporal lobe epilepsy is controversial. Prospective studies of human febrile seizures have found no adverse effects on the developing brain. However, adults with temporal lobe epilepsy and associated limbic cell loss frequently have a history of prolonged febrile seizures in early life. These critical issues may be resolved using appropriate animal models. Published models of hyperthermic seizures have used 'adolescent' and older rats, have yielded a low percentage of animals with actual seizures, or have suffered from a high mortality, rendering them unsuitable for long-term studies. This article describes the establishment of a model of febrile seizures using the infant rat. Hyperthermia was induced by a regulated stream of mildly heated air, and the seizures were determined by both behavioral and electroencephalographic (EEG) criteria. Stereotyped seizures were generated in 93.6% of 10-11-day-old rats. EEG correlates of these; seizures were not evident in cortical recordings, but were clearly present in depth recordings from the amygdala and hippocampus. Prolonged febrile seizures could be induced without bums, yielding a low mortality (11%) and long-term survival. In summary, an infant rat paradigm of EEG-confirmed, hyperthermia-induced seizures which is suitable for long-term studies is described. This model should be highly valuable for studying the mechanisms and sequelae of febrile seizures.

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“…In contrast, immature rats appear resistant to the brain damaging effect of status epilepticus. Several investigators have attempted to produce epileptic brain damage in developing rats by the use of a variety of convulsant drugs (bicuculline, fluorothyl, kainic acid) as well as sequential electroshock (11)(12)(13)(20)(21)(22). Collectively, the results of these studies indicate that, despite status epilepticus of 90 min or more, rat pups less than 20 d of postnatal age remain free of brain damage, whereas those which are.…”

Section: Blood Glucose Concentrationsmentioning

confidence: 99%

“…On the othe~. hand, both published and unpublished experimental studies in immature animals of most, although not all, species have failed to demonstrate that even prolonged seizures (status epilepticus) lead to overt brain injury (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] (see "Discussion").…”

mentioning

confidence: 99%