ArticleAnnals of clinical and translational neurology2015
Diazepam effect during early neonatal development correlates with neuronal Cl(.).
Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Neonatal seizures and GABAergic drugs: Scylla and Charybdis?Epilepsia open · 2026Review
- Recurrent neonatal seizures increase tonic inhibition and respond to enhancers of δ-containing GABAA receptors.JCI insight · 2025Article
- Enhancing GABAergic Tonic Inhibition Reduces Seizure-Like Activity in the Neonatal Mouse Hippocampus and Neocortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
- Why won't it stop? The dynamics of benzodiazepine resistance in status epilepticus.Nature reviews. Neurology · 2022Review
- Generational sensitivity alteration in Chironomus yoshimatsui to carbamate and pharmaceutical chemicals and the effect on Catalase, CYP450, and hemoglobin gene transcription.Ecotoxicology (London, England) · 2021Article
- Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.Neurobiology of disease · 2019Article
- Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential.Trends in neurosciences · 2017Review
- Developmental Decrease of Neuronal Chloride Concentration Is Independent of Trauma in Thalamocortical Brain Slices.PloS one · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveAlthough benzodiazepines and other GABAA receptors allosteric modulators are used to treat neonatal seizures, their efficacy may derive from actions on subcortical structures. Side effects of benzodiazepines in nonseizing human neonates include myoclonus, seizures, and abnormal movements. Excitatory actions of GABA may underlie both side effects and reduced anticonvulsant activity of benzodiazepines. Neocortical organotypic slice cultures were used to study: (1) spontaneous cortical epileptiform activity during early development; (2) developmental changes in [Cl(-)]i and (3) whether diazepam's anticonvulsant effect correlated with neuronal [Cl(-)]i.
methodsEpileptiform activity in neocortical organotypic slice cultures was measured by field potential recordings. Cl(-) changes during development were assessed by multiphoton imaging of neurons transgenically expressing a Cl-sensitive fluorophore. Clinically relevant concentrations of diazepam were used to test the anticonvulsant effectiveness at ages corresponding to premature neonates through early infancy.
results(1) Neocortical organotypic slices at days in vitro 5 (DIV5) exhibited spontaneous epileptiform activity. (2) Epileptiform event duration decreased with age. (3) There was a progressive decrease in [Cl(-)]i over the same age range. (4) Diazepam was ineffective in decreasing epileptiform activity at DIV5-6, but progressively more effective at older ages through DIV15. (5) At DIV5-6, diazepam worsened epileptiform activity in 50% of the slices.
interpretationThe neocortical organotypic slice is a useful model to study spontaneous epileptiform activity. Decreasing [Cl(-)]i during development correlates with decreasing duration of spontaneous epileptiform activity and increasing anticonvulsant efficacy of diazepam. We provide a potential explanation for the reports of seizures and myoclonus induction by benzodiazepines in newborn human neonates and the limited electrographic efficacy of benzodiazepines for the treatment of neonatal seizures.
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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.