ReviewEpilepsia2014
Pharmacotherapeutic targeting of cation-chloride cotransporters in neonatal seizures.
Review in Epilepsia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 127 citations in OpenAlex.
- Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.Translational psychiatry · 2020Trial
- A Preliminary Study Evaluating the Safety and Efficacy of Bumetanide, an NKCC1 Inhibitor, in Patients with Drug-Resistant Epilepsy.CNS drugs · 2019Trial
- "Molecular Shakers" as Transmembrane Single-Molecule Channels Toward 1:1 ClAngewandte Chemie (International ed. in English) · 2026Article
- The First 30 Days Postnatal of the GABA Receptor: A Comprehensive Overview.Molecular neurobiology · 2025Review
- An Evaluation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Carbamazepine-Resistant Rats.International journal of molecular sciences · 2025Article
- Restoring Compromised ClThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Heterogeneous subpopulations of GABAiScience · 2024Article
- Serine 937 phosphorylation enhances KCC2 activity and strengthens synaptic inhibition.Scientific reports · 2023Article
- Review
- Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Loop diuretics association with Alzheimer's disease risk.Frontiers in aging · 2023Article
- Role of Monovalent Ions in the NKCC1 Inhibition Mechanism Revealed through Molecular Simulations.International journal of molecular sciences · 2022Article
- Structural Pharmacology of Cation-Chloride Cotransporters.Membranes · 2022Review
- Article
- hUC-MSC-mediated recovery of subacute spinal cord injury through enhancing the pivotal subunits β3 and γ2 of the GABATheranostics · 2022Article
- Bumetanide Effects on Resting-State EEG in Tuberous Sclerosis Complex in Relation to Clinical Outcome: An Open-Label Study.Frontiers in neuroscience · 2022Article
- Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention.Frontiers in integrative neuroscience · 2022Review
- The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner.PLoS biology · 2022Article
- Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model.Science signaling · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Seizures are a common manifestation of acute neurologic insults in neonates and are often resistant to the standard antiepileptic drugs that are efficacious in children and adults. The paucity of evidence-based treatment guidelines, coupled with a rudimentary understanding of disease pathogenesis, has made the current treatment of neonatal seizures empiric and often ineffective, highlighting the need for novel therapies. Key developmental differences in γ-aminobutyric acid (GABA)ergic neurotransmission between the immature and mature brain, and trauma-induced alterations in the function of the cation-chloride cotransporters (CCCs) NKCC1 and KCC2, probably contribute to the poor efficacy of standard antiepileptic drugs used in the treatment of neonatal seizures. Although CCCs are attractive drug targets, bumetanide and other existing CCC inhibitors are suboptimal because of pharmacokinetic constraints and lack of target specificity. Newer approaches including isoform-specific NKCC1 inhibitors with increased central nervous system penetration, and direct and indirect strategies to enhance KCC2-mediated neuronal chloride extrusion, might allow therapeutic modulation of the GABAergic system for neonatal seizure treatment. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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What OpenQuestion holds
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.