The Repeated Flurothyl Seizure Model in Mice

Abstract

Development of spontaneous seizures is the hallmark of human epilepsy. There is a critical need for new epilepsy models in order to elucidate mechanisms responsible for leading to the development of spontaneous seizures and for testing new anti-epileptic compounds. Moreover, rodent models of epilepsy have clearly demonstrated that there are two independent seizure systems in the brain: 1) the forebrain seizure network required for the expression of clonic seizures mediated by forebrain neurocircuitry, and 2) the brainstem seizure network necessary for the expression of brainstem or tonic seizures mediated by brainstem neurocircuitry. In seizure naïve animals, these two systems are separate, but developing models that can explore the intersection of the forebrain and brainstem seizure systems or for elucidating mechanisms responsible for bringing these two seizure systems together may aid in our understanding of: 1) how seizures can become more complex overtime, and 2) sudden unexpected death in epilepsy (SUDEP) since propagation of seizure discharge from the forebrain seizure system to the brainstem seizure system may have an important role in SUDEP because many cardiorespiratory systems are localized in the brainstem. The repeated flurothyl seizure model of epileptogenesis, as described here, may aid in providing insight into these important epilepsy issues in addition to understanding how spontaneous seizures develop.

RNA Polymerase 1 Is Transiently Regulated by Seizures and Plays a Role in a Pharmacological Kindling Model of Epilepsy

“…Indeed, reduced levels of de-novo synthesized 18S and 28S rRNA were observed in cytoplasmic rat cerebrocortical RNA that was isolated for up to 90 min after flurothyl-induced seizures [48]. Of note, similarly to PTZ, pro-convulsant effects of flurothyl are due to inhibition of the GABA-A receptors and are limited to a single, short-lasting seizure episode [51]. Similarly to our current findings in the mouse PTZ model, nascent rRNA levels normalized to control values at 6 h after flurothyl-induced seizures in rats [48].…”

GABAergic neurons are susceptible to BAX-dependent apoptosis following isoflurane exposure in the neonatal period

“…To investigate whether neonatal exposure to anesthesia influenced seizure susceptibility, we used a flurothyl exposure paradigm as previously described [ 25 , 26 ]. Gad2 IRES-Cre/+ ; Bax Flox/Flox ; R26 TdTom/TdTom and Gad2 IRES-Cre/+ ; Bax Flox/+ ; R26 TdTom/TdTom animals were exposed to isoflurane or control conditions on PND7, then returned to their home cages and allowed to age until undergoing seizure susceptibility testing during postnatal week (PNW) 7–8 as previously described [ 25 , 26 ]. Briefly, animals were placed in an enclosed cylindrical chamber 6 inches in diameter and 10 inches tall with a physically isolated vaporization chamber.…”

Open-source system for millisecond-synchronized continuous video-EEG

“…After the extinction of pain responses, we implanted the Epoch radio-telemetry EEG transmitter (BIOPAC Systems Inc., Goleta, California) according to the protocol previously described 8 . Seizures were induced using the flurothyl model, according to the protocol of Ferland 9 . Mice were group-housed in an approved satellite facility with ad libitum food, water, and a running wheel.…”