ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
The chloride transporter Na(+)-K(+)-Cl- cotransporter isoform-1 contributes to intracellular chloride increases after in vitro ischemia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 128 citations in OpenAlex.
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.Life (Basel, Switzerland) · 2025Review
- Seizures May Worsen Outcomes of Neonatal Hypoxic-Ischemic Encephalopathy: A Longitudinal Serum Biomarkers Study.Pediatric neurology · 2025Article
- Modulation of GABAergic System in a Chicken Retinal Ischemic Model: The Role of Chloride Cotransporters.Journal of neuroscience research · 2025Article
- Timing of interventions to control neuronal chloride elevation in a model of neonatal seizures after hippocampal injury.Epilepsia · 2024Article
- Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.CNS neuroscience & therapeutics · 2024Article
- Article
- Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen-Glucose Deprivation Conditions.Current issues in molecular biology · 2024Article
- Hyperchloremia and Hypernatremia Decreased Microglial and Neuronal Survival during Oxygen-Glucose Deprivation/Reperfusion.Biomedicines · 2024Article
- Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.Acta pharmaceutica Sinica. B · 2023Article
- Cerebrospinal Fluid Chloride Is Associated with Disease Activity of Relapsing-Remitting Multiple Sclerosis: A Retrospective Cohort Study.Brain sciences · 2023Article
- Role of NKCC1 and KCC2 during hypoxia-induced neuronal swelling in the neonatal neocortex.Neurobiology of disease · 2023Article
- Recent advance in dual-functional luminescent probes for reactive species and common biological ions.Analytical and bioanalytical chemistry · 2022Review
- The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology.Frontiers in physiology · 2022Review
- Treating Seizures after Hypoxic-Ischemic Encephalopathy-Current Controversies and Future Directions.International journal of molecular sciences · 2021Review
- Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies.International journal of molecular sciences · 2021Review
- Intricacies of GABAInternational journal of molecular sciences · 2021Review
- LRRC8A-dependent volume-regulated anion channels contribute to ischemia-induced brain injury and glutamatergic input to hippocampal neurons.Experimental neurology · 2020Article
- Intracellular ClPflugers Archiv : European journal of physiology · 2020Review
- Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation.Brain sciences · 2019Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Ischemic episodes in the CNS cause significant disturbances in neuronal ionic homeostasis. To directly measure changes in intracellular Cl- concentration ([Cl-]i) during and after ischemia, we used Clomeleon, a novel ratiometric optical indicator for Cl-. Hippocampal slices from adult transgenic mice expressing Clomeleon in hippocampal neurons were subjected to 8 min of oxygen-glucose deprivation (OGD) (an in vitro model for ischemia) and reoxygenated in the presence of glucose. This produced mild neuronal damage 3 h later that was prevented when the extracellular [Cl-] was maintained at 10 mm during reoxygenation. OGD induced a transient decrease in fluorescence resonance energy transfer within Clomeleon, indicating an increase in [Cl-]i. During reoxygenation, there was a partial recovery in [Cl-]i, but [Cl-]i rose again 45 min later. To investigate sources of Cl- accumulation, we examined the effects of Cl- transport inhibitors on the rises in [Cl-]i during and after OGD. Bumetanide and furosemide, which inhibit Cl- influx through the Na(+)-K(+)-Cl- cotransporter isoform-1 (NKCC-1) and efflux through the K(+)-Cl- cotransporter isoform-2, were unable to inhibit the first rise in [Cl-]i, yet entirely prevented the secondary rise in [Cl-]i during reoxygenation. In contrast, picrotoxin, which blocks the GABA-gated Cl- channel, did not inhibit the secondary rise in [Cl-]i after OGD. [Cl-]i increases during reoxygenation were accompanied by an increase in phosphorylation of NKCC-1, an indication of increased NKCC-1 activity after OGD. We conclude that NKCC-1 plays an important role in OGD-induced Cl- accumulation and subsequent neuronal damage.
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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.