Effects of diltiazem on hyperthermia induced seizures in the rat pup

Laorden, María‐Luisa; Carrillo, Evaristo; Miralles, F; Puig, Margarita M.

doi:10.1016/0306-3623(90)90829-b

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…Importantly, neither of these two doses had a detectable effect on the baseline breath rate, and hyperthermia was associated with a similar increase in breath rate in rats injected with 50-150 mg/kg and in those injected with saline ( Figure 5B). As could be expected (Hirtz and Nelson, 1983;Laorden et al, 1990), a higher dose of diazepam (2.5 mg/kg) prevented seizure generation in four of four rats tested, while the saline-injected control animals showed robust eFS ( Figure 5A). At this concentration, diazepam suppressed the breath rate under control conditions and, under hyperthermia, only a modest increase in breathing was seen in the presence of the drug ( Figure 5B).…”

Section: Lack Of Electrographic Fs In Ca VII Ko Micesupporting

confidence: 85%

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

Ruusuvuori¹,

Huebner²,

Kirilkin³

et al. 2013

EMBO J

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Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13–14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13–P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS.

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Section: Lack Of Electrographic Fs In Ca VII Ko Micesupporting

confidence: 85%

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

Ruusuvuori¹,

Huebner²,

Kirilkin³

et al. 2013

EMBO J

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“…Previous hypotheses about febrile seizure generation have included enhanced NMDA receptor-mediated glutamate transmission (Morimoto et al, 1993, 1995) and changes in calcium homeostasis (Laorden et al, 1990). However, whether these mechanisms are directly involved in HT seizure generation has been considered controversial (Baram, 2002), because the pharmacological agents used to prevent HT-induced seizures in these studies also increased the threshold temperature for seizure onset.…”

Section: Discussionmentioning

confidence: 99%

A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors

Hunt

Hortopan

Gillespie

et al. 2012

Experimental Neurology

121

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Febrile seizures are the most common seizure type in children under the age of five, but mechanisms underlying seizure generation in vivo remain unclear. Animal models to address this issue primarily focus on immature rodents heated indirectly using a controlled water bath or air blower. Here we describe an in vivo model of hyperthermia-induced seizures in larval zebrafish aged 3 to 7 days post-fertilization (dpf). Bath controlled changes in temperature are rapid and reversible in this model. Acute electrographic seizures following transient hyperthermia showed age-dependence, strain independence, and absence of mortality. Electrographic seizures recorded in the larval zebrafish forebrain were blocked by adding antagonists to the transient receptor potential vanilloid (TRPV4) channel or N-methyl-d-aspartate (NMDA) glutamate receptor to the bathing medium. Application of GABA, GABA re-uptake inhibitors, or TRPV1 antagonist had no effect on hyperthermic seizures. Expression of vanilloid channel and glutamate receptor mRNA was confirmed by quantitative PCR analysis at each developmental stage in larval zebrafish. Taken together, our findings suggest a role of heat-activation of TRPV4 channels and enhanced NMDA receptor-mediated glutamatergic transmission in hyperthermia-induced seizures.

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“…Moreover, cortical maturation is incomplete during the second postnatal week in the rat, resulting in poorly organized and low-voltage cortical EEG activity [4,31]. Nevertheless, published studies of infant rat hyperthermic seizures have lacked EEG data [9,16,20,21] or have documented only low voltage, semi-rhythmic cortical EEG ( [28], in the five-day-old rat).…”

Section: Discussionmentioning

confidence: 99%

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

Baram

Gerth

Schultz

1997

Developmental Brain Research

229

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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Effects of diltiazem on hyperthermia induced seizures in the rat pup

Cited by 7 publications

References 24 publications

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors

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

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