Evidence map›Paper›PMID 31394959›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2020

Modeling hyperosmotic blood-brain barrier opening within human tissue-engineered in vitro brain microvessels.

Raleigh M Linville, Jackson G DeStefano, Matt B Sklar, Chengyan Chu, Piotr Walczak, Peter C Searson

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, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
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  3. Permeability Benchmarking: Guidelines for ComparingJournal of chemical information and modeling · 2025
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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 1 institution in 1 country.

Raleigh M LinvilleInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Jackson G DeStefanoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Matt B SklarInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Chengyan ChuDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Piotr WalczakDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-5417-0828
Johns Hopkins University · US

Funding

BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
Mechanisms of cerebrovascular barrier dysfunction caused by APP and PSEN1 mutations and amyloid beta exposureR01NS106008 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2019 to 2023
$1.9M
Treatment of ALS based on transplantation of glial restricted progenitorsR01NS091110 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WALCZAK, PIOTR · 2015 to 2019
$1.8M
NIGMS NIH HHS T32 GM007057NINDS NIH HHS R01 NS091110NINDS NIH HHS R01 NS106008
6 · The paper itself

Abstract

As the majority of therapeutic agents do not cross the blood-brain barrier (BBB), transient BBB opening (BBBO) is one strategy to enable delivery into the brain for effective treatment of CNS disease. Intra-arterial infusion of the hyperosmotic agent mannitol reversibly opens the BBB; however, widespread clinical use has been limited due to the variability in outcomes. The current model for mannitol-induced BBBO assumes a transient but homogeneous increase in permeability; however, the details are poorly understood. To elucidate the mechanism of hyperosmotic opening at the cellular level, we developed a tissue-engineered microvessel model using stem cell-derived human brain microvascular endothelial cells (BMECs) perturbed with clinically relevant mannitol doses. This model recapitulates physiological shear stress, barrier function, microvessel geometry, and cell-matrix interactions. Using live-cell imaging, we show that mannitol results in dose-dependent and spatially heterogeneous increases in paracellular permeability through the formation of transient focal leaks. Additionally, we find that the degree of BBB opening and subsequent recovery is modulated by treatment with basic fibroblast growth factor. These results show that tissue-engineered BBB models can provide insight into the mechanisms of BBBO and hence improve the reproducibility of hyperosmotic therapies for treatment of CNS disease.

Indexed as

Models, AnatomicTissue EngineeringBlood-Brain BarrierCapillary PermeabilityDose-Response Relationship, DrugFluorescent DyesHumansMannitolMicroscopy, Phase-ContrastMicrovesselsOsmosisFluorescent DyesMannitolBlood–brain barrierhyperosmotic blood–brain barrier openingmannitolmicrovesselsthree-dimensional in vitro models

Identifiers

PMID31394959
PMCPMC7308510
OpenAlexW2968722124

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.