ArticlePLoS biology2022
The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 37 citations in OpenAlex.
- Citalopram Neuroendocrine Challenge Shows Altered Tryptophan and Kynurenine Metabolism in Migraine.Cells · 2022Trial
- Combined use of Bumetanide and MGE cell transplantation alleviates neuropathic pain and its mechanism after spinal cord injury in mice.Frontiers in immunology · 2026Article
- Focal cortical dysplasias: modeling pediatric drug-resistant epilepsy using human brain organoids.Frontiers in cellular neuroscience · 2026Review
- The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.Science advances · 2025Article
- Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage.Brain, behavior, & immunity - health · 2024Article
- Heterogeneous subpopulations of GABAiScience · 2024Article
- SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.CNS neuroscience & therapeutics · 2024Article
- Research on the innate immune response in transgenic mice following ischemic stroke.Frontiers in aging neuroscience · 2024Review
- Bumetanide induces post-traumatic microglia-interneuron contact to promote neurogenesis and recovery.Brain : a journal of neurology · 2023Article
- Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1.Fluids and barriers of the CNS · 2023Article
- The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases.Molecular and cellular biochemistry · 2023Review
- 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
- Layer-specific changes of KCC2 and NKCC1 in the mouse dentate gyrus after entorhinal denervation.Frontiers in molecular neuroscience · 2023Article
- Article
- Article
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
- Nanoformulated Bumetanide Ameliorates Social Deficiency in BTBR Mice Model of Autism Spectrum Disorder.Frontiers in immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1β (IL-1β), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema and worse neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.
Indexed as
Identifiers
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.