ArticleJournal of neuroinflammation2022
Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Efficacy of bumetanide in animal models of ischemic stroke: a systematic review and meta-analysis.Aging · 2024Pooled it
- Post-hemorrhagic hydrocephalus of prematurity is associated with disruption of tight junctions and increased macrophage activity in the choroid plexus.Fluids and barriers of the CNS · 2026Article
- Pharmacological inhibition of SPAK-NKCC1 complex attenuates astrogliosis and restores cerebral blood flow in a mouse model of VCID.Acta neuropathologica communications · 2025Article
- Choroid Plexus Fibroblast-ILC2 Niche Promotes Adult Hippocampal Neurogenesis after Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol.Nature communications · 2025Article
- Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- Oxidative stress-induced NCC activation in the development of nocturnal polyuria in mice: Therapeutic potential of a sustained hydrogen-releasing silicon-based agent.Biochemistry and biophysics reports · 2025Article
- The Role of Gut Microbiota in Blood-Brain Barrier Disruption after Stroke.Molecular neurobiology · 2024Review
- The Blood-Cerebrospinal Fluid Barrier Dysfunction in Brain Disorders and Stroke: Why, How, What For?Neuromolecular medicine · 2024Review
- Carotid artery vascular stenosis causes the blood-CSF barrier damage and neuroinflammation.Journal of neuroinflammation · 2024Article
- Modulation of Cerebrospinal Fluid Dysregulation via a SPAK and OSR1 Targeted Framework Nucleic Acid in Hydrocephalus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.CNS neuroscience & therapeutics · 2024Article
- Molecular Crowding: Physiologic Sensing and Control.Annual review of physiology · 2024Review
- Cation Chloride Cotransporter NKCC1 Operates through a Rocking-Bundle Mechanism.Journal of the American Chemical Society · 2024Article
- Identification of m6A-Related Biomarkers in Systemic Lupus Erythematosus: A Bioinformation-Based Analysis.Journal of inflammation research · 2024Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier.Frontiers in cellular neuroscience · 2023Article
- Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice.Neurochemistry international · 2023Article
- Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundThe mechanisms underlying dysfunction of choroid plexus (ChP) blood-cerebrospinal fluid (CSF) barrier and lymphocyte invasion in neuroinflammatory responses to stroke are not well understood. In this study, we investigated whether stroke damaged the blood-CSF barrier integrity due to dysregulation of major ChP ion transport system, Na
methodsSham or ischemic stroke was induced in C57Bl/6J mice. Changes on the SPAK-NKCC1 complex and tight junction proteins (TJs) in the ChP were quantified by immunofluorescence staining and immunoblotting. Immune cell infiltration in the ChP was assessed by flow cytometry and immunostaining. Cultured ChP epithelium cells (CPECs) and cortical neurons were used to evaluate H
resultsIschemic stroke stimulated activation of the CPECs apical membrane SPAK-NKCC1 complex, NF-κB, and MMP9, which was associated with loss of the blood-CSF barrier integrity and increased immune cell infiltration into the ChP. Oxidative stress directly activated the SPAK-NKCC1 pathway and resulted in apoptosis, neurodegeneration, and NKCC1-mediated ion influx. Pharmacological blockade of the SPAK-NKCC1 pathway protected the ChP barrier integrity, attenuated ChP immune cell infiltration or neuronal death.
conclusionStroke-induced pathological stimulation of the SPAK-NKCC1 cascade caused CPECs damage and disruption of TJs at the blood-CSF barrier. The ChP SPAK-NKCC1 complex emerged as a therapeutic target for attenuating ChP dysfunction and lymphocyte invasion after stroke.
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.