Evidence map›Paper›PMID 40592323›Full record

ArticleCell2025

Deconstructing the intercellular interactome in vascular dementia with focal ischemia for therapeutic applications.

Min Tian, Riki Kawaguchi, Yang Shen, Michal Machnicki, Nikole G Villegas, Delaney R Cooper, Natalia Montgomery, Ying Cai, Jacqueline Haring, Ruirui Lan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Serpine2-Lrp1 and CD39-ANeuroscience bulletin · 2026
    Article
  10. Article
  11. Article
  12. Bitopic AJournal of medicinal chemistry · 2025
    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

18 authors.

Min TianDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Riki KawaguchiDepartment of Psychiatry and Biobehavioral Sciences, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Yang ShenNeurobiology, Psychiatry, and Psychology Departments and Integrative Center for Learning and Memory, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Michal MachnickiDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Nikole G VillegasDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Delaney R CooperDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Natalia MontgomeryDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ying CaiNeurobiology, Psychiatry, and Psychology Departments and Integrative Center for Learning and Memory, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Jacqueline HaringDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ruirui LanDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Angelina H YuanDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Christopher K WilliamsDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Shino MagakiDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Harry V VintersDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ye ZhangDepartment of Psychiatry and Biobehavioral Sciences, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Lindsay M De BiaseDepartment of Physiology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Alcino J SilvaNeurobiology, Psychiatry, and Psychology Departments and Integrative Center for Learning and Memory, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
S Thomas CarmichaelDepartment of Neurology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: scarmichael@mednet.ucla.edu.

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peyman Golshani, SUMA JACOB · 2020 to 2026
$9.6M
Defining the molecular spectrum of white matter vascular lesionsRF1NS139972 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS, HINMAN, JASON D · 2024 to 2024
$4.7M
Mechanisms of White Matter Repair in Subcortical White Matter IschemiaR37NS102185 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS · 2018 to 2024
$2.8M
The role of pericytes in scar formation following stroke and myocardial infarctionR01NS112256 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS · 2020 to 2024
$2.2M
NICHD NIH HHS P50 HD103557NINDS NIH HHS R01 NS112256NINDS NIH HHS R37 NS102185NINDS NIH HHS RF1 NS139972
6 · The paper itself

Abstract

Vascular dementia (VaD), the second-leading cause of dementia, is primarily a white matter ischemic disease with no direct therapies. Cell-cell interactions within lesion sites dictate disease progression or repair. To elucidate key intercellular pathways, we employ a VaD mouse model with focal ischemia replicating many elements of the complex pathophysiology of human VaD combined with transcriptomic and functional analyses. By integrating cell-type-specific mouse VaD transcriptomes and human VaD single-nucleus RNA sequencing (snRNA-seq) data plus a custom ligand-receptor database (4,053 human and 2,032 mouse pairs), conserved dysregulated intercellular pathways in both species are identified. We demonstrate that two intercellular signaling systems, Serpine2-Lrp1 and CD39-A3AR, are disrupted in VaD. Reduced Serpine2 expression enhances oligodendrocyte progenitor cell (OPC) differentiation, promoting repair, while an A3AR-specific agonist-currently in clinical trials for psoriasis-restores tissue integrity and behavioral function in the VaD model. This study reveals intercellular signaling targets and provides a foundation for developing innovative therapies for VaD.

Indexed as

Brain IschemiaDementia, VascularAnimalsCell CommunicationCell DifferentiationDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLOligodendrocyte Precursor CellsSignal TransductionTranscriptomeA3ARadenosine receptor 3CD39cell-cell interactionglialearning and memoryligand-receptor pairsL-R pairsmotor deficitSerpine2stroketissue repairVaDvascular dementiawhite matterWM

Identifiers

PMID40592323
PMCPMC12221338

What OpenQuestion holds

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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.