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Absence seizures in the GAERS model: subthalamic nucleus stimulation
Published in Hans O Lüders, Deep Brain Stimulation and Epilepsy, 2020
Alim-Louis Benabid, Laurent Vercueil, Karine Bressand, Maurice Dematteis, Abdelhamid Benazzouz, Lorella Minotti, Philippe Kahane
GAERS rats are an interesting model with EEG and behavioral aspects similar to human absence epilepsy. Absence seizures in this model are suppressed by all antiabsence drugs. Absence seizures occur spontaneously, have a duration of approximately 20 seconds, and are characterized by generalized spike and wave discharges (SWD), concomitant with behavioral arrest.7 The epileptiform discharges are facilitated by noradrenergic and dopaminergic decrements and GABAergic increments. They are suppressed by ethosuximide and other antiabsence drugs, but are exacerbated by phenytoin and other anticonvulsant drugs. Progress in the understanding of the role of the basal ganglia in the control of seizures has been advanced using this genetic model of generalized non-convulsive seizures.8 The cortex and the reticular nucleus and the ven-trobasal relay nuclei of the thalamus play an important role in the development of SWD.
Third Histamine Receptor: From Discovery to Clinics, Long-Lasting Love Story at INSERM and Bioprojet
Published in Divya Vohora, The Third Histamine Receptor, 2008
To settle this question, we asked Dr. Depaulis—belonging to a reputed group in Strasbourg expert in rodent seizures—to study tiprolisant on some of their models. This group is particularly known for having developed a rat genetic model of human epilepsy (particularly of absence epilepsy in children and adults), the Genetic Absence Epilepsy, Rat from Strasbourg (GAERS). On this animal model, tiprolisant diminished the number and duration of spike-and-wave discharges by up to 77%, that is, characteristic EEG changes of the disorder.
Cenobamate tablets as a treatment for focal-onset seizures in adults
Published in Expert Review of Clinical Pharmacology, 2021
CNB was effective in several established preclinical rodent seizure and epilepsy models that are sought to reflect both focal and generalized epileptogenesis. CNB was efficacious in the including the rat and mouse maximal electroshock seizure (MES) test as a model for generalized tonic-clonic seizures, in the mouse subcutaneous pentylenetetrazol (PTZ) and picrotoxin but not bicuculline seizure models of myoclonic seizures, the mouse 6-Hz psychomotor seizure model of refractory epilepsy, and the rat hippocampal kindling model of focal seizures [25,26,29,32]. Furthermore, efficacy in the genetic absence epilepsy rats from Strasbourg (GAERS) animal model was reported [25]. This profile along with a comparison with the effects of other antiseizure medications in these preclinical models may suggest a broad-spectrum clinical efficacy (29) which has to be investigated in upcoming clinical trials beyond focal epileptogenesis.
Morphological, biochemical, and histopathological effects of levetiracetam on pregnant albino rats and their offspring
Published in Ultrastructural Pathology, 2023
Safaa M. H. Abdelaziz, Ranya Mohammed Abdelgalil, Shaimaa R. Abdelmohsen
These results were similar to Sudhishma et al.,43 who observed that exposure to levetiracetam (270 mg/kg) throughout pregnancy and breastfeeding caused cognitive impairment in rats’ offspring. Also, the current study was similar to a recent study that examined the effects of in utero exposure to levetiracetam on the offspring of GAERS (Genetic Absence Epilepsy Rats from Strasbourg).44 The authors noticed that the lungs of the levetiracetam-exposed offsprings had thicker alveolar epithelium in the majority of areas, which suggested impaired alveoli formation. Some renal corpuscles had dilated Bowman’s gaps, which might be interpreted as a negative effect of levetiracetam on the kidney.
Novel and emerging therapeutics for genetic epilepsies
Published in Expert Review of Neurotherapeutics, 2021
Ana Pejčić, Slobodan M. Janković, Miralem Đešević, Refet Gojak, Snežana Lukić, Nenad Marković, Miloš Milosavljević
CX-8998 ((R)-2-(4-isopropylphenyl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide) is potent, selective, and state-dependent blocker of Cav3 T-type of calcium channels [113,133]. This investigational compound has shown significant efficacy in experimental rat models of tremor, generalized epilepsy, and neuropathic pain [134–136]. CX-8998 was also shown to be effective in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of epilepsy [137]. It showed dose-dependent reduction of both number and cumulative duration of spike-wave discharges and near-complete suppression (99%) of seizure activity during the post-dose recording period [137]. The results of several phase I, pharmacokinetic studies, as well as the results of phase II trial in schizophrenic patients, showed that CX-8998 was well-tolerated, with mild to moderate transient adverse effects [133]. Initially, a phase II study of CX-8998 for generalized epileptic syndromes with absence seizures was planned as a double-blind, randomized, placebo-controlled, parallel-group study [138,139]. However, in the end, this study was conducted as an open-label study (NCT03406702) which enrolled 15 patients aged 16–55 years with a clinical diagnosis of idiopathic generalized epilepsy with absence seizures (including, but not limited to, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, or epilepsy with eyelid myoclonias) resistant to at least two previous antiepileptic drugs appropriate for the patient’s epilepsy syndrome [140]. This study consisted of a 4-week screening period and 4-week dose-titration period, followed by a 1-week safety monitoring period after the last administered dose of CX-8998 [140]. The study results are pending. The most important findings will be data on the incidence of treatment-emergent adverse events, changes from baseline in significant electrocardiogram parameters, changes from baseline in clinical safety laboratory assessments, etc. [140].