Evidence map›Paper›PMID 32955153›Full record

ArticleGlia2021

Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain.

Benjamin P Heithoff, Kijana K George, Aubrey N Phares, Ivan A Zuidhoek, Carmen Munoz-Ballester, Stefanie Robel

Open access · greenAbstract read
In one paragraph

Article in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
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

179 citing papers in PubMed, 245 citations in OpenAlex.

  1. Article
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  7. Astrocytes in Multiple Sclerosis: Getting to the Core.International journal of molecular sciences · 2026
    Review
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  11. Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  12. Review
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  15. Article
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  17. bioRxiv : the preprint server for biology · 2026
    Article
  18. Review
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  20. Review

119 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Benjamin P HeithoffFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0001-7276-6441
Kijana K GeorgeFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0002-2459-9500
Aubrey N PharesFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0001-9449-6534
Ivan A ZuidhoekFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0003-3355-1215
Carmen Munoz-BallesterFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0002-2298-7753
Stefanie RobelFralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.ORCID 0000-0001-6716-3670
Biomedical Research Institute · USCarilion Roanoke Memorial Hospital · US

Funding

Evaluating astrocyte loss after traumatic brain injury in initiation of post-traumatic epilepsyR01NS105807 · NINDS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI ROBEL, STEFANIE · 2018 to 2022
$1.9M
NINDS NIH HHS R01 NS105807
6 · The paper itself

Abstract

In the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier (BBB) properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the BBB. To determine if astrocytes contribute a nonredundant and necessary function in maintaining the adult BBB, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hr. Indicative of BBB damage, leakage of the small molecule Cadaverine, and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial nonproliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes 1 month after ablation. In conclusion, astrocytes are necessary to maintain BBB integrity in the adult brain. BBB-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss.

Indexed as

AstrocytesBlood-Brain BarrierAnimalsBrainCadaverineMiceTamoxifenCadaverineTamoxifenastrogliosiscontact inhibitionglial scargliovascular unittight junctions

Identifiers

PMID32955153
PMCPMC7736206
OpenAlexW3087458297

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.