Evidence map›Paper›PMID 31757960›Full record

ArticleNature communications2019

Brain-to-cervical lymph node signaling after stroke.

Elga Esposito, Bum Ju Ahn, Jingfei Shi, Yoshihiko Nakamura, Ji Hyun Park, Emiri T Mandeville, Zhanyang Yu, Su Jing Chan, Rakhi Desai, Ayumi Hayakawa and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing 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

81 citing papers in PubMed.

  1. Review
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  9. The cribriform plate: A dynamic central nervous system-immune hub.The Journal of experimental medicine · 2026
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  16. Science advances · 2025
    Article
  17. The glymphatic system in Huntington's disease.Journal of Huntington's disease · 2025
    Review
  18. Article
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  20. Review

21 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

13 authors.

Elga EspositoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Bum Ju AhnNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Jingfei ShiNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Yoshihiko NakamuraNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-2297-2885
Ji Hyun ParkNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Emiri T MandevilleNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-7680-0923
Zhanyang YuNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Su Jing ChanNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0001-7166-9658
Rakhi DesaiNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Ayumi HayakawaNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Xunming JiChina-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
Eng H LoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Lo@helix.mgh.harvard.edu.
Kazuhide HayakawaNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. khayakawa1@mgh.harvard.edu.

Funding

Proteomic Profiling of Patent Foramen Ovale Related Neurovascular InjuryR01NS067139 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2010 to 2023
$3.7M
Thrombolysis Profiles in tPA ResponseR01NS093415 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H., NING, MINGMING · 2015 to 2019
$1.9M
Inflammatory Mechanisms of Brain - Lymphatic Signaling in StrokeR01NS099620 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HAYAKAWA, KAZUHIDE, LO, ENG H. · 2016 to 2020
$1.9M
Glycoproteomics in Ischemic Stroke Related HyperglycemiaR21NS113065 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2020 to 2020
$462k
NINDS NIH HHS R01 NS067139NINDS NIH HHS R01 NS093415NINDS NIH HHS R01 NS099620NINDS NIH HHS R21 NS113065
6 · The paper itself

Abstract

After stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.

Indexed as

AnimalsBrainBrain InfarctionBrain IschemiaCell ProliferationEndothelial CellsEndothelium, LymphaticInflammationLymphangiogenesisLymph NodesMacrophagesMiceNeckRatsStrokeVascular Endothelial Growth Factor CVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3

Identifiers

PMID31757960
PMCPMC6876639

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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.