ArticleCell2023
The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus.
2 registry-linked trialsOpen access · greenAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 101 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 1 pooled it
19.7field-weighted citation impact, top 1% of its field
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.
A Prospective, Multi-center, Open-label Study to Observe the Efficacy and Safety of Rapamycin in the Treatment of Communicating Hydrocephalus Secondary to Intraventricular Hemorrhage
NCT07662174 phase1 / phase2not yet recruitingnot on this mapstarted 2027, after this paper: background citation
VENTURE-PHH: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- CSF hypersecretion versus impaired CSF absorption in posthemorrhagic hydrocephalus: a systematic review.Acta neurochirurgica · 2023Pooled it
- Phosphoproteomic Insights into TRPV4-AMPK Signaling Axis and Barrier Regulation in the Choroid Plexus Epithelium.International journal of molecular sciences · 2026Article
- Leptomeningeal fibroblasts promote glioblastoma progression by regulating cerebrospinal fluid dynamics.Nature communications · 2026Article
- Pathological mutation L241P in Kir7.1 channel inhibits its activity in the choroid plexus epithelium and decreases cerebrospinal fluid KJournal of physiology and biochemistry · 2026Article
- Exploring and translating novel approaches targeting the choroid plexus for the treatment of hydrocephalus: a literature review.Fluids and barriers of the CNS · 2026Review
- The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV.PLoS pathogens · 2026Review
- Cytokine markers in intracerebral hemorrhage are linked to ventricular imaging and outcomes.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2026Article
- Review
- Clinical features, risk factors and outcomes of hydrocephalus in neonatal bacterial meningitis: a retrospective case-control study.Scientific reports · 2026Article
- Inhibition of the Microglial cGAS-STING Pathway Improves Neurological Deficits and Long-Term Hydrocephalus Symptoms in Mice with Intraventricular Hemorrhage.Molecular neurobiology · 2026Article
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Targeting ATP11B-YAP axis repairs mitochondrial function and inhibits neuronal ferroptosis to attenuate age-related cognitive decline.Signal transduction and targeted therapy · 2026Article
- 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
- Neutrophil-to-lymphocyte ratio and the risk of cerebrospinal fluid diversion after posterior fossa tumor resection in pediatrics.Neurosurgical review · 2026Article
- Adenosine APurinergic signalling · 2026Article
- Macrostructural, microstructural, and cellular effects of neuroinflammation on the mouse brain.Brain, behavior, & immunity - health · 2026Article
- Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins.Nature neuroscience · 2026Article
- [A novel strategy for the diagnosis and treatment of complex hydrocephalus in children: A staged surgical management protocol].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Automated Ventricle Assessment via Three-dimensional Anatomical Reconstruction (AVA-TAR): a computational toolkit for autonomous lateral ventricle assessment in preclinical hydrocephalus models.bioRxiv : the preprint server for biology · 2026Article
- The potential of platelet-rich plasma and PRP-derived biologics for neurological disorders: mechanisms and translational research.Frontiers in immunology · 2026Review
41 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
37 authors at 14 institutions in 3 countries.
Stephanie M RobertDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Benjamin C ReevesDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Emre KiziltugDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Phan Q DuyDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Jason K KarimyDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
M Shahid MansuriDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Arnaud MarlierDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Garrett AllingtonDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Ana B W GreenbergDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Tyrone DeSpenzaDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Amrita K SinghDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Xue ZengDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Kedous Y MekbibDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Adam J KundishoraDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Carol Nelson-WilliamsDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Le Thi HaoDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Jinwei ZhangInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter EX1 2LU, UK.
TuKiet T LamDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, CT 06520, USA.
Rashaun WilsonDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, CT 06520, USA.
William E ButlerDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Michael L DilunaDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Philip FeinbergDepartment of Neurobiology, Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School, Worcester, MA 01655, USA; Medical Scientist Training Program, UMass Chan Medical School, Worcester, MA 01655, USA.
Dorothy P SchaferDepartment of Neurobiology, Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
Kiavash MovahediLaboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, 1050 Brussels, Belgium.
Allen TannenbaumDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 11794, USA.
Sunil KoundalDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06520, USA.
Xinan ChenDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Helene BenvenisteDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06520, USA.
David D LimbrickDepartment of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Steven J SchiffDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Murat GunelDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
J Marc SimardDepartment of Neurosurgery, University of Maryland, School of Medicine, Baltimore, MD 21201, USA; Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
Richard P LiftonLaboratory of Human Genetics and Genomics, the Rockefeller University, New York, NY 10065, USA.
Seth L AlperDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Eric DelpireDepartment of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Kristopher T KahleDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA; Department of Neurosurgery and Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. Electronic address: kahle.kristopher@mgh.harvard.edu.
Yale University · USHarvard University · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USNeuropsychiatric Research Institute · USRockefeller University · USStony Brook University · USUniversity of Exeter · GBUniversity of Maryland, Baltimore · USUniversity of Massachusetts Chan Medical School · USVanderbilt University · USVIB-UGent Center for Inflammation Research · BEWashington University in St. Louis · USW. M. Keck Foundation · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MOverall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3MHuman Genetics and Molecular Mechanisms of Congenital HydrocephalusR01NS111029 · NINDS · YALE UNIVERSITY · PI DENIZ, ENGIN, JIN, SHENG CHIH · 2020 to 2024
$2.5MModulation of Choroid Plexus Immuno-secretory Function to Restore Cerebrospinal Fluid Homeostasis in HydrocephalusR01NS109358 · NINDS · YALE UNIVERSITY · PI Kristopher T. Kahle · 2018 to 2026
$2.4MNCI NIH HHS P30 CA008748NICHD NIH HHS P50 HD103537NINDS NIH HHS R01 NS109358NINDS NIH HHS R01 NS111029
Abstract
The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highly similar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSF production from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinase SPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.
Indexed as
Choroid PlexusHydrocephalusBlood-Brain BarrierBrainCytokine Release SyndromeHumansImmunity, Innateblood-CSF barriercerebrospinal fluidchoroid plexusCSFhydrocephalusneuro-inflammationNKCC1SPAK
Identifiers
What Socratic holds
Textmetadata
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Read underepoch 390
Registered trials
NCT06563817ClinicalTrials.gov
NCT07662174ClinicalTrials.gov
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 Socratic graph.