ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 174 citations in OpenAlex.
- A Preliminary Study Evaluating the Safety and Efficacy of Bumetanide, an NKCC1 Inhibitor, in Patients with Drug-Resistant Epilepsy.CNS drugs · 2019Trial
- Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs.BMC veterinary research · 2013Trial
- Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy.Biomedicines · 2025Review
- An Evaluation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Carbamazepine-Resistant Rats.International journal of molecular sciences · 2025Article
- Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Imbalanced expression of cation-chloride cotransporters as a potential therapeutic target in an Angelman syndrome mouse model.Scientific reports · 2023Article
- Scoping review of disease-modifying effect of drugs in experimental epilepsy.Frontiers in neurology · 2023Article
- Unilateral optogenetic kindling of hippocampus leads to more severe impairments of the inhibitory signaling in the contralateral hippocampus.Frontiers in molecular neuroscience · 2023Article
- Developmental changes in brain activity of heterozygousFrontiers in neurology · 2023Article
- Article
- Selected Molecular Targets for Antiepileptogenesis.International journal of molecular sciences · 2021Review
- Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss.International journal of molecular sciences · 2021Review
- Targeting the pH Paradigm at the Bedside: A Practical Approach.International journal of molecular sciences · 2020Review
- Preventing neuronal edema increases network excitability after traumatic brain injury.The Journal of clinical investigation · 2020Article
- Contribution of Monocarboxylate Transporter 6 to the Pharmacokinetics and Pharmacodynamics of Bumetanide in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Review
- Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?Epilepsia · 2020Review
- Screening for Efficacious Anticonvulsants and Neuroprotectants in Delayed Treatment Models of Organophosphate-induced Status Epilepticus.Neuroscience · 2020Article
- Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis.Frontiers in neurology · 2020Review
12 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that changes in neuronal chloride homeostasis may be involved in the mechanisms by which brain insults induce the development of epilepsy. A variety of brain insults, including status epilepticus (SE), lead to changes in the expression of the cation-chloride cotransporters KCC2 and NKCC1, resulting in intracellular chloride accumulation and reappearance of immature, depolarizing synaptic responses to GABA(A) receptor activation, which may critically contribute to the neuronal hyperexcitability underlying epileptogenesis. In the present study, it was evaluated whether prolonged administration of the selective NKCC1 inhibitor, bumetanide, after a pilocarpine-induced SE modifies the development of epilepsy in adult female rats. The antiepileptic drug phenobarbital, either alone or in combination, was used for comparison. Based on pharmacokinetic studies with bumetanide, which showed extremely rapid elimination and low brain penetration of this drug in rats, bumetanide was administered systemically with different dosing protocols, including continuous intravenous infusion. As shown by immunohistochemistry, neuronal NKCC1 expression was markedly upregulated shortly after SE. Prophylactic treatment with phenobarbital after SE reduced the number of rats developing spontaneous seizures and decreased seizure frequency, indicating a disease-modifying effect. Bumetanide did not exert any significant effects on development of spontaneous seizures nor did it enhance the effects of phenobarbital. However, combined treatment with both drugs counteracted several of the behavioral consequences of SE, which was not observed with single drug treatment. These data do not indicate that bumetanide can prevent epilepsy after SE, but the disease-modifying effect of this drug warrants further studies with more lipophilic prodrugs of bumetanide.
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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.