ArticleThe European journal of neuroscience2015
Acute TrkB inhibition rescues phenobarbital-resistant seizures in a mouse model of neonatal ischemia.
Article in The European journal of neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
- Age-related impact of phenobarbital in suppressing prenatal alcohol exposure-related seizures in developing rats.Alcohol (Fayetteville, N.Y.) · 2025Article
- High Doses of ANA12 Improve Phenobarbital Efficacy in a Model of Neonatal Post-Ischemic Seizures.International journal of molecular sciences · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model.Science signaling · 2021Article
- The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia.Metabolic brain disease · 2021Review
- Novel Therapeutics for Neonatal Seizures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Brain-Derived Neurotrophic Factor in Neonatal Seizures.Pediatric neurology · 2021Review
- Partial Activation of TrkB Receptors Corrects Interneuronal Calcium Channel Dysfunction and Reduces Epileptogenic Activity in Neocortex following Injury.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- TrkB agonists prevent postischemic emergence of refractory neonatal seizures in mice.JCI insight · 2020Article
- Rescue of PB-resistant neonatal seizures with single-dose of small-molecule TrkB antagonist show long-term benefits.Epilepsy research · 2020Article
- Oxygen-Glucose Deprivation Differentially Affects Neocortical Pyramidal Neurons and Parvalbumin-Positive Interneurons.Neuroscience · 2019Article
- Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters.Cells · 2019Review
- Role of NKCC1 and KCC2 in Epilepsy: From Expression to Function.Frontiers in neurology · 2019Review
- Pharmaco-resistant Neonatal Seizures: Critical Mechanistic Insights from a Chemoconvulsant Model.Developmental neurobiology · 2018Article
- Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal seizures by ANA12.Scientific reports · 2018Article
- Neonatal Seizures: Impact on Neurodevelopmental Outcomes.Frontiers in pediatrics · 2015Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Neonatal seizures are commonly associated with hypoxic-ischemic encephalopathy. Phenobarbital (PB) resistance is common and poses a serious challenge in clinical management. Using a newly characterized neonatal mouse model of ischemic seizures, this study investigated a novel strategy for rescuing PB resistance. A small-molecule TrkB antagonist, ANA12, used to selectively and transiently block post-ischemic BDNF-TrkB signaling in vivo, determined whether rescuing TrkB-mediated post-ischemic degradation of the K(+)-Cl(-) co-transporter (KCC2) rescued PB-resistant seizures. The anti-seizure efficacy of ANA12 + PB was quantified by (i) electrographic seizure burden using acute continuous video-electroencephalograms and (ii) post-treatment expression levels of KCC2 and NKCC1 using Western blot analysis in postnatal day (P)7 and P10 CD1 pups with unilateral carotid ligation. ANA12 significantly rescued PB-resistant seizures at P7 and improved PB efficacy at P10. A single dose of ANA12 + PB prevented the post-ischemic degradation of KCC2 for up to 24 h. As anticipated, ANA12 by itself had no anti-seizure properties and was unable to prevent KCC2 degradation at 24 h without follow-on PB. This indicates that unsubdued seizures can independently lead to KCC2 degradation via non-TrkB-dependent pathways. This study, for the first time as a proof-of-concept, reports the potential therapeutic value of KCC2 modulation for the management of PB-resistant seizures in neonates. Future investigations are required to establish the mechanistic link between ANA12 and the prevention of KCC2 degradation.
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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.