ArticleCNS neuroscience & therapeutics2015
Acute and chronic efficacy of bumetanide in an in vitro model of posttraumatic epileptogenesis.
Article in CNS neuroscience & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 21 citations in OpenAlex.
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies.Biomedicines · 2022Review
- CurrentCurrent opinion in biomedical engineering · 2020Article
- Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery.IEEE transactions on bio-medical engineering · 2019Article
- ECS Dynamism and Its Influence on Neuronal Excitability and Seizures.Neurochemical research · 2019Review
- Transient ischemia facilitates neuronal chloride accumulation and severity of seizures.Annals of clinical and translational neurology · 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
- Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation.Neuroscience and biobehavioral reviews · 2018Review
- Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential.Trends in neurosciences · 2017Review
- Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures.Neural regeneration research · 2017Article
- Epileptogenesis in organotypic hippocampal cultures has limited dependence on culture medium composition.PloS one · 2017Article
- Staged anticonvulsant screening for chronic epilepsy.Annals of clinical and translational neurology · 2016Article
- Pubertal Expression of α4βδ GABAA Receptors Reduces Seizure-Like Discharges in CA1 Hippocampus.Scientific reports · 2016Article
- Diazepam effect during early neonatal development correlates with neuronal Cl(.).Annals of clinical and translational neurology · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
backgroundSeizures triggered by acute injuries to the developing brain respond poorly to first-line medications that target the inhibitory chloride-permeable GABAA receptor. Neuronal injury is associated with profound increases in cytoplasmic chloride ([Cl(-)]i) resulting in depolarizing GABA signaling, higher seizure propensity and limited efficacy of GABAergic anticonvulsants. The Na(+)-K(+)-2Cl(-) (NKCC1) cotransporter blocker bumetanide reduces [Cl(-)]i and causes more negative GABA equilibrium potential in injured neurons. We therefore tested both the acute and chronic efficacy of bumetanide on early posttraumatic ictal-like epileptiform discharges and epileptogenesis.
methodsAcute hippocampal slices were used as a model of severe traumatic brain injury and posttraumatic epileptogenesis. Hippocampal slices were then incubated for 3 weeks. After a 1-week latent period, slice cultures developed chronic spontaneous ictal-like discharges. The anticonvulsant and anti-epileptogenic efficacy of bumetanide, phenobarbital, and the combination of these drugs was studied.
resultsBumetanide reduced the frequency and power of early posttraumatic ictal-like discharges in vitro and enhanced the anticonvulsant efficacy of phenobarbital. Continuous 2-3 weeks administration of bumetanide as well as phenobarbital in combination with bumetanide failed to prevent posttraumatic ictal-like discharges and epileptogenesis.
conclusionsOur data demonstrate a persistent contribution of NKCC1 cotransport in posttraumatic ictal-like activity, presumably as a consequence of chronic alterations in neuronal chloride homeostasis and GABA-mediated inhibition. New strategies for more effective reduction in posttraumatic and seizure-induced [Cl(-)]i accumulation could provide the basis for effective treatments for posttraumatic epileptogenesis and the resultant seizures.
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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.