Pharmacological Assessment of Anti-seizure Medications in the Rat Amygdala-kindling model2.15.0.02.15.0.0
Abstract number :
1.397
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2024
Submission ID :
769
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Corinne Roucard, PhD – SynapCell SAS
Eloïse Gronlier, PhD – SynapCell SAS
Chloé Habermacher, PhD – SynapCell SAS
Baptiste Caraballo, BS – SynapCell SAS
Carine Dumont, BS – SynapCell SAS
Yann Roche, PhD – SynapCell SAS
Julien Volle, PhD – SynapCell SAS
Rationale: Despite advances in epilepsy treatment, unmet clinical needs persist, particularly in patients who exhibit resistance to anti-seizure medications (ASMs). Preclinical models are crucial for early drug discovery and the development of therapies for symptomatic epilepsy treatment. The rat amygdala-kindling model, characterized by repetitive subconvulsive electrical stimulations, provides valuable insights into epilepsy progression. This model predicts drug efficacy in seizure control, from focal to secondarily generalized convulsive seizures. In this study, we evaluated the pharmacological profiles of various ASMs using this model.
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Methods: Sprague Dawley rats were implanted with electrodes in the basolateral amygdala (BLA), parietal cortex, and prefrontal cortex. Epileptic activity was assessed via electroencephalogram (EEG) recordings and synchronized video monitoring. Afterdischarges (ADs), defined as EEG spikes and spike-waves following stimulation, were used to determine the AD threshold (ADT) for each rat. The kindling protocol was administered daily until rats reached stage 5 on Racine's scale for three consecutive days. Rats were alternately treated with ASMs (or respective vehicles): diazepam, ethosuximide, carbamazepine, retigabine, and levetiracetam.
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Results: diazepam (3 mg/kg) effectively reduced motor components of seizures and afterdischarge duration (ADD). Ethosuximide (100 mg/kg) had no impact on seizure motor components or ADD. Distinct effects were observed between focal and cortical EEG responses for the remaining three ASMs.
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Conclusions: This study highlights the translational relevance of the rat amygdala-kindling model for identifying novel compounds with improved tolerability and efficacy against focal and secondarily generalized seizures. Combining this model with a cross-over design offers a decision-enabling screening platform for epilepsy prevention and treatment, particularly in cases of pharmacoresistant focal seizures.
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Funding: Project CORTEX - iNov by France 2030
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Anti-seizure Medications