Dose-Dependent Induction of Differential Seizure Phenotypes by Pilocarpine in Rats: Considerations for Translational Potential DOI Creative Commons
Dolika D. Vasović, Olivera Stanojlović, Dragan Hrnčić

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(10), P. 1579 - 1579

Published: Sept. 26, 2024

Background and Objectives: Pilocarpine is used in experimental studies for testing antiepileptic drugs, but further characterization of this model essential its usage novel drugs. The aim our study was to the behavioral EEG characteristics acute seizures caused by different doses pilocarpine rats. Materials Methods: Male Wistar rats were treated with a single intraperitoneal dose 100 mg/kg (P100), 200 (P200), or 300 (P300) pilocarpine, epileptiform behavior changes followed within 4 h. Results: intensity duration significantly higher P300 vs. P200 P100 groups, status epilepticus dominating self-limiting tonic–clonic group. seizure grade group only during first hour after application. latency shorter compared Conclusions: (200 mg/kg) can be as suitable initial screening potential anti-seizure medications, while at mg/kg, it mechanisms epileptogenesis.

Language: Английский

New epilepsy therapies in development DOI
Pavel Klein, Rafal M. Kaminski, Matthias J. Koepp

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(9), P. 682 - 708

Published: July 22, 2024

Language: Английский

Citations

27
Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature DOI Creative Commons
Jamir Pitton Rissardo, Ana Letícia Fornari Caprara

Medicina, Journal Year: 2023, Volume and Issue: 59(8), P. 1389 - 1389

Published: July 28, 2023

Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri®, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency Ontozry® Arvelle Therapeutics Netherlands B.V.(Amsterdam, Neatherlands) in March 2021. medication that could potentially change perspectives regarding management prognosis of refractory epilepsy. this way, study aims to review literature on CNB's pharmacological properties, pharmacokinetics, efficacy, safety. CNB highly effective drug managing onset seizures, with more than twenty percent individuals drug-resistant epilepsy achieving seizure freedom. This finding remarkable antiseizure literature. mechanism action still poorly understood, but it associated transient persistent sodium currents GABAergic neurotransmission. animal studies, showed sustained efficacy potency 6 Hz test regardless stimulus intensity. was revealed be most cost-effective among different third-generation medications. Also, have neuroprotective effects. However, there are concerns its potential abuse suicidality risk, which future studies should clearly assess, after protocols changed. major drawback therapy slow complex titration maintenance phases preventing wide use new agent clinical practice.

Language: Английский

Citations

14
Current advances in rodent drug-resistant temporal lobe epilepsy models: Hints from laboratory studies DOI
Shuo Zhang,

Shengyang Xie,

Yang Zheng

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 174, P. 105699 - 105699

Published: Feb. 19, 2024

Language: Английский

Citations

5
Revisiting the concept of drug‐resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force DOI
Stéphane Auvin, Aristea S. Galanopoulou, Solomon L. Moshé

et al.

Epilepsia, Journal Year: 2023, Volume and Issue: 64(11), P. 2891 - 2908

Published: Sept. 7, 2023

Abstract Despite progress in the development of anti‐seizure medications (ASMs), one third people with epilepsy have drug‐resistant (DRE). The working definition DRE, proposed by International League Against Epilepsy (ILAE) 2010, helped identify individuals who might benefit from presurgical evaluation early on. As incidence DRE remains high, TASK1 workgroup on ILAE/American Society (AES) Joint Translational Task Force discussed heterogeneity and complexity its presentation mechanisms, confounders drawing mechanistic insights when testing treatment responses, barriers modeling across lifespan translating species. We propose that it is necessary to revisit current order transform preclinical clinical research mechanisms biomarkers, novel, effective, precise, pharmacologic treatments, allowing for earlier recognition drug resistance individualized therapies.

Language: Английский

Citations

12
Of Mice and Men: The Inter-individual Variability of the Brain's Response to Drugs DOI Creative Commons
Wolfgang Löscher

eNeuro, Journal Year: 2024, Volume and Issue: 11(2), P. ENEURO.0518 - 23.2024

Published: Feb. 1, 2024

Biological variation is ubiquitous in nature. Despite highly standardized breeding and husbandry under controlled environmental conditions, phenotypic diversity exists laboratory mice rats just as it does humans. The resulting inter-individual variability affects various characteristics of animal disease models, including the responsiveness to drugs. Thus, common practice averaging data within an experimental group can lead misinterpretations neuroscience other research fields. In this commentary, impact drug illustrated by examples from testing antiseizure medications rodent temporal lobe epilepsy models. Individual rendered epileptic treatment according protocols fall into groups that either do or not respond medications, thus mimicking clinical situation patients with epilepsy. Population responses are normally distributed, divergent responding concealed averages subjected parametric statistical tests. Genetic, epigenetic, factors believed contribute response but specific molecular physiological causes well understood. Being aware rodents allows improved interpretation both behavioral phenotypes effects a pharmacological experiment.

Language: Английский

Citations

4
A multicenter Phase II randomized, placebo-controlled single-blind trial with the SV2A ligand seletracetam in photosensitive epilepsy patients DOI Creative Commons

Dorothée Kasteleijn‐Nolst Trenité,

Armel Stockis, Édouard Hirsch

et al.

Epilepsy & Behavior, Journal Year: 2025, Volume and Issue: 164, P. 110241 - 110241

Published: Jan. 18, 2025

Language: Английский

Citations

0
Neonatal febrile seizures: Dimethyl itaconate’s role in behavioral recovery and glutathione enzyme modulation in adult rats DOI Creative Commons
Zohreh Ghotbeddin, Mohammad Ali Farboodniay Jahromi, Ali Shahriari

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0318430 - e0318430

Published: March 25, 2025

Febrile seizures are common in children and can lead to neurological deficits like motor impairments, memory problems, cognitive decline. Research on dimethyl itaconate aims mitigate these effects improve the quality of life for affected people. By exploring its potential as a protective agent against oxidative stress during seizures, this study adult male rats measures activity key enzymes related behavioral performance. Pregnant were divided into control, sham, DMI, febrile seizure, DMI + seizure groups. Seizure severity was evaluated through threshold frequency measurements, while memory, function, balance assessed using shuttle box, rotarod, open field, wire hanging tests. After that, hippocampus tissue removed from brain levels MDA, SOD, GSH, TAC, GR, GPx, catalase measured biochemical methods. Results show that raised reduced tonic-clonic seizures. The group also showed improved movement, compared (p < 0.05 all cases). Overall, decreased outcomes fever-affected rats.

Language: Английский

Citations

0
Levetiracetam-Induced Seizure Aggravation-case series and literature review DOI Creative Commons

Tal Friedman‐Korn,

Tal Benoliel Berman,

Diya Doufish

et al.

Seizure, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Do Seizures Damage the Brain ?—Cumulative Effects of Seizures and Epilepsy: A 2025 Perspective DOI Open Access

Pavel Klein,

Enrique Carrazana, Tracy A. Glauser

et al.

Epiliepsy currents/Epilepsy currents, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

In 1885, William Gowers proposed that epilepsy is a progressive disease, based on clinical evidence before any effective treatments were available. His long-standing hypothesis has been summarized with the statement “seizures beget seizures.” Whether this case and related questions about seizure-induced modification damage of brain circuits are fundamental importance for neurobiological understanding epilepsy, development treatment strategies, management, prognostication. Consensus progression remained controversial. Here, we critically review these questions, incorporating perspectives perceived inconsistencies in past studies, potential implications recent longitudinal imaging cognitive emphasize experimental gaps have proved challenging. Answers to important management strategies achieve prompt acute control seizures prevention their recurrence long-term comorbidities.

Language: Английский

Citations

0
Current challenges in focal epilepsy treatment: An Italian Delphi consensus DOI Creative Commons
Giancarlo Di Gennaro, Simona Lattanzi, Oriano Mecarelli

et al.

Epilepsy & Behavior, Journal Year: 2024, Volume and Issue: 155, P. 109796 - 109796

Published: April 21, 2024

BackgroundEpilepsy, a globally prevalent neurological condition, presents distinct challenges in management, particularly for focal-onset types. This study aimed at addressing the current and perspectives focal epilepsy with focus on Italian reality.MethodsUsing Delphi methodology, this research collected analyzed level of consensus panel experts key aspects care. Areas included patient flow, treatment pathways, controlled versus uncontrolled epilepsy, follow-up protocols, relevance patient-reported outcomes (PROs). method allowed comprehensive assessment divergences clinical opinions practices.ResultsThe achieved 23 out 26 statements, three items failing to reach consensus. There was strong agreement importance timely intervention, individualized plans, regular follow-ups Epilepsy Centers, role PROs practice. In cases there clear inclination pursue alternative options following failure two previous therapies. Divergent views were evident inclusion surgery routine necessity EEG evaluations follow-ups. Other findings concerns about lack pediatric-specific limiting therapeutic population, insufficient attention transition from pediatric adult care, need improved communication. The results highlighted complexities managing broad care aspects, yet notable specific management approaches.ConclusionThe offered valuable insights into state epilepsy. It many deficiencies pathway reality, while it also underscored patient-centric early appropriate approaches. called continued research, policy development, healthcare system improvements enhance highlighting ongoing tailored solutions evolving field.

Language: Английский

Citations

2