Evidence map›Paper›PMID 29589805›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019

Hyaluronan impairs the barrier integrity of brain microvascular endothelial cells through a CD44-dependent pathway.

Abraham J Al-Ahmad, Ronak Patel, Sean P Palecek, Eric V Shusta

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Targeted proteomic analysis identifies ACVRL1 as a marker of cerebral edema in aneurysmal subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Article
  5. GlioblastomaACS biomaterials science & engineering · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. The Brain and Spinal Microvasculature in Normal Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. CD44 mediates shear stress mechanotransduction in an in vitro blood-brain barrier model through small GTPases RhoA and Rac1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    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

4 authors at 2 institutions in 1 country.

Abraham J Al-Ahmad1 Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Ronak Patel2 Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
Sean P Palecek1 Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Eric V Shusta1 Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Texas Tech University · USUniversity of Wisconsin–Madison · US

Funding

RXRalpha and PPARdelta Signaling as Novel Regulators of the Blood-Brain BarrierR01NS083688 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SHUSTA, ERIC V · 2013 to 2017
$1.9M
NINDS NIH HHS R01 NS083688
6 · The paper itself

Abstract

Hyaluronan (HA) constitutes the most abundant extracellular matrix component during brain development, only to become a minor component rapidly after birth and in adulthood to remain in specified regions. HA signaling has been associated with several neurological disorders, yet the impact of HA signaling at the blood-brain barrier (BBB) function remains undocumented. In this study, we investigated the impact of HA on BBB properties using human-induced pluripotent stem cell (iPSC) -derived and primary human and rat BMECs. The impact of HA signaling on developmental and mature BMECs was assessed by measuring changes in TEER, permeability, BMECs markers (GLUT1, tight junction proteins, P-gp) expression and localization, CD44 expression and hyaluronan levels. In general, HA treatment decreased barrier function and reduced P-gp activity with effects being more prominent upon treatment with oligomeric forms of HA (oHA). Such effects were exacerbated when applied during BMEC differentiation phase (considered as developmental BBB). We noted a hyaluronidase activity as well as an increase in CD44 expression during prolonged oxygen-glucose deprivation stress. Inhibition of HA signaling by antibody blockade of CD44 abrogated the detrimental effects of HA treatment. These results suggest the importance of HA signaling through CD44 on BBB properties.

Indexed as

AnimalsBlood-Brain BarrierBrainCapillary PermeabilityCell LineCells, CulturedEndothelial CellsHumansHyaluronan ReceptorsHyaluronic AcidInduced Pluripotent Stem CellsRatsRats, Sprague-DawleyTight JunctionsCD44 protein, humanHyaluronan ReceptorsHyaluronic AcidBlood–brain barrierhyaluronanpermeabilitystem cellstight junctions

Identifiers

PMID29589805
PMCPMC6727144
OpenAlexW2795217332

What OpenQuestion holds

Textmetadata
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.