Increased frequency of interleukin-1β (−511) allele 2 in febrile seizures

Virta, Maarit; Hurme, Mikko; Helminen, Merja

doi:10.1016/s0887-8994(01)00380-0

Cited by 118 publications

(94 citation statements)

References 19 publications

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“…Thus the IL-1β produced by LPS fever and excitation by KA could ultimately synergize to increase excitability past a threshold that initiates and maintains behavioral convulsions, through a recently documented modulatory effect of IL-1β on N-methyl-Daspartate (NMDA) receptor function (46). This potential role of IL-1β in FCs has been recognized previously (47), and is an area that has received a considerable amount of attention recently (40,41,(48)(49)(50). Therefore this model, by incorporating an immune challenge and physiologic fever, may allow further investigation into this relation.…”

Section: Discussionmentioning

confidence: 93%

“…For example, it has been suggested that brain arginine vasopressin released as an antipyretic may contribute to the genesis of febrile convulsions (72,73). The physiologic fever used in this model may aid in the elucidation of these mechanisms that may involve immune reaction products (e.g., cytokines) produced in the brain (40,41,(47)(48)(49). Thus by attempting to closely mimic the human clinical characteristics of FCs, this model will allow the examination of the short-and long-term affects of FCs on the brain and its development.…”

Section: Discussionmentioning

confidence: 99%

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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: 93%

Section: Discussionmentioning

confidence: 99%

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

2004

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“…Febrile seizures have been shown to be associated with increased IL-1β levels in CNS and blood plasma (68,69), and such IL-1β levels associated with a genetic polymorphism (70,71). IL-1β can act on the interleukin receptors on astrocytes and via the transcription factor NFκB induce a variety of molecules including the chemokines, cytokines and ERM proteins that are up-regulated in the sclerotic hippocampus.…”

Section: An Integrating Hypothesismentioning

confidence: 99%

Gene Expression in Temporal Lobe Epilepsy is Consistent with Increased Release of Glutamate by Astrocytes

Lee

Mane

Eid

et al. 2007

Mol Med

117

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Patients with temporal lobe epilepsy (TLE) often have a shrunken hippocampus that is known to be the location in which seizures originate. The role of the sclerotic hippocampus in the causation and maintenance of seizures in temporal lobe epilepsy (TLE) has remained incompletely understood despite extensive neuropathological investigations of this substrate. To gain new insights and develop new testable hypotheses on the role of sclerosis in the pathophysiology of TLE, the differential gene expression profile was studied. To this end, DNA microarray analysis was used to compare gene expression profiles in sclerotic and nonsclerotic hippocampi surgically removed from TLE patients. Sclerotic hippocampi had transcriptional signatures that were different from non-sclerotic hippocampi. The differentially expressed gene set in sclerotic hippocampi revealed changes in several molecular signaling pathways, which included the increased expression of genes associated with astrocyte structure (glial fibrillary acidic protein, ezrin-moesin-radixin, palladin), calcium regulation (S100 calcium binding protein beta, chemokine (C-X-C motif) receptor 4) and blood-brain barrier function (Aquaaporin 4, Chemokine (C-C-motif) ligand 2, Chemokine (C-C-motif) ligand 3, Plectin 1, intermediate filament binding protein 55kDa) and inflammatory responses. Immunohistochemical localization studies show that there is altered distribution of the gene-associated proteins in astrocytes from sclerotic foci compared with nonsclerotic foci. It is hypothesized that the astrocytes in sclerotic tissue have activated molecular pathways that could lead to enhanced release of glutamate by these cells. Such glutamate release may excite surrounding neurons and elicit seizure activity.

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“…In two overlapping reports 8,12 from Kanemoto et al, we retained the one 8 with the largest and more recent sample size. Healthy controls included in the studies of Virta et al 9 and Peltola et al 38 were the same, thus they were counted once. Finally, 13 references met our criteria for inclusion ( Table 1).…”

Section: Study Inclusion and Characteristicsmentioning

confidence: 99%