Evidence map›Paper›PMID 39537986›Full record

ArticleTranslational stroke research2025

Development and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease.

Grace Prochilo, Chuanlong Li, Eleni Miliotou, Russell Nakasone, Alissa Pfeffer, Charles Beaman, Naoki Kaneko, David S Liebeskind, Jason D Hinman

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational stroke research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

9 authors.

Grace ProchiloDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.ORCID http://orcid.org/0000-0002-7137-1912
Chuanlong LiDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Eleni MiliotouDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Russell NakasoneDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Alissa PfefferDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Charles BeamanDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Naoki KanekoDepartment Radiology, David Geffen School of Medicine, The University of California, Los Angeles, Los Angeles, CA, USA.
David S LiebeskindDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA.
Jason D HinmanDepartment of Neurology, David Geffen School of Medicine, Gordon Neuroscience Research Building, The University of California, 635 Charles E. Young Dr. South, Room 415, Los AngelesLos Angeles, CA, USA. jhinman@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-0872-5044

Funding

Shear Stress and Endothelial Pathophysiology in Intracranial AtherosclerosisR01NS112799 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HINMAN, JASON D, LIEBESKIND, DAVID SIGMUND · 2020 to 2025
$3.8M
NIH HHS NS112799NINDS NIH HHS R01 NS112799
6 · The paper itself

Abstract

Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies.

Indexed as

Cerebrovascular CirculationIntracranial ArteriosclerosisMiddle Cerebral ArteryEndothelial CellsHumansBlood flowComputational fluid dynamicsEndotheliaIntracranial atherosclerosisStroke

Identifiers

PMID39537986
PMCPMC12202576

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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.