Evidence map›Paper›PMID 39142282›Full record

ArticleNeuron2024

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism.

Caterina P Profaci, Sean S Harvey, Kaja Bajc, Tony Z Zhang, Danielle A Jeffrey, Alexander Z Zhang, Kelsey M Nemec, Hayk Davtyan, Carleigh A O'Brien, Gabriel L McKinsey and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Mr BMT Achieves Systemic Macrophage Replacement With Preservation of Tissue Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Cholesterol Drives IFITM3CNS neuroscience & therapeutics · 2026
    Article
  6. Article
  7. CD157Stem cell reports · 2026
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Development of the blood-brain barrier.Development (Cambridge, England) · 2026
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Caterina P ProfaciDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA. Electronic address: cprofaci@scripps.edu.
Sean S HarveyDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.
Kaja BajcDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.
Tony Z ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.
Danielle A JeffreyDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Alexander Z ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.
Kelsey M NemecDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hayk DavtyanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
Carleigh A O'BrienDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gabriel L McKinseyDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Aaron LongworthDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Timothy P McMullenDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Joia K CapocchiInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
Jessica G GonzalezDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Devon A LawsonDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Thomas D ArnoldDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Dimitrios DavalosDepartment of Neurosciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Mathew Blurton-JonesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Fabrice DabertrandDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
F Chris BennettDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Richard DanemanDepartment of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.

Funding

PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM007635 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI DELL'ACQUA, MARK L · 1985 to 2023
$6.1M
Blood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4M
Capillary control of cerebral blood flow, and its disruption in small vessel diseaseR01HL136636 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Fabrice Dabertrand · 2017 to 2026
$3.8M
Gliovascular Mechanisms of Blood-Brain Barrier Disruption in Neuroinflammatory DiseaseR01NS112526 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI DAVALOS, DIMITRIOS · 2019 to 2023
$2.4M
Rescuing neurovascular coupling to protect neuronal plasticity and cognitionRF1NS129022 · NINDS · UNIVERSITY OF COLORADO DENVER · PI DABERTRAND, FABRICE, DELL'ACQUA, MARK L · 2022 to 2022
$1.8M
Rescuing neurovascular coupling to protect neuronal plasticity and cognitionR01NS129022 · NINDS · UNIVERSITY OF COLORADO DENVER · PI MARK L DELL'ACQUA, Fabrice Dabertrand · 2025 to 2026
$1.1M
Neuroimmunology Training Program at the University of California, IrvineT32NS121727 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green, Thomas E Lane · 2022 to 2026
$854k
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
Microglial regulation of cerebrovascular cholesterol metabolism: implications forAlzheimers diseaseR21AG067035 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DANEMAN, RICHARD · 2020 to 2020
$434k
Pericyte KATP channel hyperactivity in cerebral small vessel diseaseF31HL170645 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI JEFFREY, DANIELLE A · 2023 to 2025
$120k
Does Pdlim1 drive blood-brain barrier dysfunction during neurological disease?F31NS110403 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PROFACI, CATERINA P · 2018 to 2020
$76k
NHLBI NIH HHS F31 HL170645NHLBI NIH HHS R01 HL136636NHLBI NIH HHS T32 HL086344NIA NIH HHS R21 AG067035NIGMS NIH HHS T32 GM007635NIH HHS S10 OD026929NINDS NIH HHS F31 NS110403NINDS NIH HHS R01 NS112526NINDS NIH HHS R01 NS129022NINDS NIH HHS RF1 NS129022NINDS NIH HHS T32 NS121727
6 · The paper itself

Abstract

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

Indexed as

Blood-Brain BarrierBrainCholesterolEndothelial CellsMicrogliaAnimalsMaleMiceMice, Inbred C57BLOrganic ChemicalsReceptors, Granulocyte-Macrophage Colony-Stimulating FactorCholesterolCsf1r protein, mouseOrganic ChemicalsPLX5622Receptors, Granulocyte-Macrophage Colony-Stimulating Factorblood-brain barriercholesterolCSF1Rendothelial cellsgenetic microglial depletionLDLRmicrogliaoff-target effectsPLX5622vasculature

Identifiers

PMID39142282
PMCPMC11446403

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Registered trials

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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.