Evidence map›Paper›PMID 35618888›Full record

ArticleMolecular psychiatry2022

Association between vascular endothelial growth factor-mediated blood-brain barrier dysfunction and stress-induced depression.

Hitomi Matsuno, Shoko Tsuchimine, Kazunori O'Hashi, Kazuhisa Sakai, Kotaro Hattori, Shinsuke Hidese, Shingo Nakajima, Shuichi Chiba, Aya Yoshimura, Noriko Fukuzato and 6 more

Abstract read
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In one paragraph

Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 3 pooled it
10.7field-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

93 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.

  1. Pooled it
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  10. [Mechanisms and intervention strategies by which neuropsychological stress promotes central nervous system tumor recurrence through bloodZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  11. A longitudinal study of CLDN5 DNA methylation and PTSD.Journal of behavioral medicine · 2026
    Article
  12. Immunity in Rodent Models of Stress.Biological psychiatry · 2026
    Review
  13. Article
  14. Molecular Characterization of the Progressive Landscape of Depression.bioRxiv : the preprint server for biology · 2026
    Article
  15. Review
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33 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

16 authors at 5 institutions in 2 countries.

Hitomi MatsunoDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. hisuzuki@ncnp.go.jp.ORCID http://orcid.org/0000-0002-8749-6760
Shoko TsuchimineDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Kazunori O'HashiDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Kazuhisa SakaiDepartment of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Kotaro HattoriDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.ORCID http://orcid.org/0000-0002-4411-2317
Shinsuke HideseDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Shingo NakajimaDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Shuichi ChibaDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Aya YoshimuraDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Noriko FukuzatoDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Mayumi KandoDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Megumi TatsumiDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Shintaro OgawaDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Noritaka IchinoheDepartment of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Hiroshi KunugiDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Kazuhiro SohyaDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. sohya@cc.saga-u.ac.jp.ORCID http://orcid.org/0000-0002-2203-440X
National Center of Neurology and Psychiatry · JPFujita Health University · JPNihon University · JPOkayama University of Science · JPSaga University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several lines of evidence suggest that stress induces the neurovascular dysfunction associated with increased blood-brain barrier (BBB) permeability, which could be an important pathology linking stress and psychiatric disorders, including major depressive disorder (MDD). However, the detailed mechanism resulting in BBB dysfunction associated in the pathophysiology of MDD still remains unclear. Herein, we demonstrate the role of vascular endothelial growth factor (VEGF), a key mediator of vascular angiogenesis and BBB permeability, in stress-induced BBB dysfunction and depressive-like behavior development. We implemented an animal model of depression, chronic restraint stress (RS) in BALB/c mice, and found that the BBB permeability was significantly increased in chronically stressed mice. Immunohistochemical and electron microscopic observations revealed that increased BBB permeability was associated with both paracellular and transcellular barrier alterations in the brain endothelial cells. Pharmacological inhibition of VEGF receptor 2 (VEGFR2) using a specific monoclonal antibody (DC101) prevented chronic RS-induced BBB permeability and anhedonic behavior. Considered together, these results indicate that VEGF/VEGFR2 plays a crucial role in the pathogenesis of depression by increasing the BBB permeability, and suggest that VEGFR2 inhibition could be a potential therapeutic strategy for the MDD subtype associated with BBB dysfunction.

Indexed as

Brain DiseasesMajor Depressive DisorderAnimalsBlood-Brain BarrierCapillary PermeabilityDepressionEndothelial CellsMiceMice, Inbred BALB CVascular Endothelial Growth Factor AVascular Endothelial Growth Factor A

Identifiers

PMID35618888
OpenAlexW4281550041

What OpenQuestion holds

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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.