ArticleAnnals of clinical and translational neurology2016
Staged anticonvulsant screening for chronic epilepsy.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Trial
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- Displacement of extracellular chloride by immobile anionic constituents of the brain's extracellular matrix.The Journal of physiology · 2025Article
- Understanding epileptogenesis from molecules to network alteration.Encephalitis (Seoul, Korea) · 2024Article
- Synthesis and Characterization of a Novel Concentration-Independent Fluorescent Chloride Indicator, ABP-Dextran, Optimized for Extracellular Chloride Measurement.Biomolecules · 2024Article
- Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine.Brain sciences · 2023Article
- The microbiota-gut-brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models.Bioengineering & translational medicine · 2022Review
- In vitro ictogenesis is stochastic at the single neuron level.Brain : a journal of neurology · 2022Article
- Novel Approaches to Prevent Epileptogenesis After Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Variability of seizure-like activity in anHeliyon · 2020Article
- Neural layer self-assembly in geometrically confined rat and human 3D cultures.Biofabrication · 2019Article
- Kinase Inhibitors with Antiepileptic Properties Identified with a Novel in Vitro Screening Platform.International journal of molecular sciences · 2019Article
- Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery.IEEE transactions on bio-medical engineering · 2019Article
- How do we use in vitro models to understand epileptiform and ictal activity? A report of the TASK1-WG4 group of the ILAE/AES Joint Translational Task Force.Epilepsia open · 2018Article
- Intrinsic Inflammation Is a Potential Anti-Epileptogenic Target in the Organotypic Hippocampal Slice Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Article
- Strengthening the Case for Epilepsy Drug Development: Bridging Experiences from the Alzheimer's Disease Field-An Opinion.Neurochemical research · 2017Review
- The Dentate Gyrus and Temporal Lobe Epilepsy: An "Exciting" Era.Epilepsy currentsArticle
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveCurrent anticonvulsant screening programs are based on seizures evoked in normal animals. One-third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high-throughput in vitro models to low-throughput in vivo models.
methodsEpileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure-like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings.
resultsWe screened 407 compound-concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy.
interpretationThe use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure-like activity and seizure-induced cell death can be easily quantified with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to find an anticonvulsant that would be missed by screening in acute models.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.