Evidence map›Paper›PMID 29570780›Full record

ArticleJournal of neurochemistry2018

Effects of ischemic post-conditioning on neuronal VEGF regulation and microglial polarization in a rat model of focal cerebral ischemia.

Elga Esposito, Kazuhide Hayakawa, Bum Ju Ahn, Su Jing Chan, Changhong Xing, Anna C Liang, Kyu-Won Kim, Ken Arai, Eng H Lo

Open access · greenAbstract read
In one paragraph

Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 55 citations in OpenAlex.

  1. New perspectives on VEGF signalling in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026
    Review
  2. Lactate modulates microglial M2 polarizationJournal of translational internal medicine · 2026
    Article
  3. Review
  4. Article
  5. VEGF and the VEGFMolecular neurobiology · 2025
    Article
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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

9 authors at 2 institutions in 4 countries.

Elga EspositoDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Kazuhide HayakawaDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Bum Ju AhnDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Su Jing ChanDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Changhong XingDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Anna C LiangDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Kyu-Won KimNeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Ken AraiDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Eng H LoDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.ORCID http://orcid.org/0000-0002-9327-2915
Harvard University · USSeoul National University · KR

Funding

Targeting ROCK for Neurogliovascular Plasticity & Remodeling After StrokeP01NS055104 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2007 to 2018
$13.3M
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
Proteomic Studies of MMP Profiles in Stroke ThrombolysisK23NS051588 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2005 to 2009
$864k
Glycoproteomics in Ischemic Stroke Related HyperglycemiaR21NS113065 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2020 to 2020
$462k
Proteomic Profile of Brain Endothelial Cell in HypoxiaR21NS052498 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2005 to 2006
$439k
Postconditioning promotes recovery in the neurovascular unit after strokeR03NS099739 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ESPOSITO, ELGA · 2017 to 2018
$168k
NINDS NIH HHS K23 NS051588NINDS NIH HHS L30 NS047252NINDS NIH HHS P01 NS055104NINDS NIH HHS R01 NS067139NINDS NIH HHS R01 NS093415NINDS NIH HHS R03 NS099739NINDS NIH HHS R21 NS052498NINDS NIH HHS R21 NS113065
6 · The paper itself

Abstract

Ischemic postconditioning is increasingly being investigated as a therapeutic approach for cerebral ischemia. However, the majority of studies are focused on the acute protection of neurons per se. Whether and how postconditioning affects multiple cells in the recovering neurovascular unit remains to be fully elucidated. Here, we asked whether postconditioning may modulate help-me signaling between injured neurons and reactive microglia. Rats were subjected to 100 min of focal cerebral ischemia, then randomized into a control versus postconditioning group. After 3 days of reperfusion, infarct volumes were significantly reduced in animals treated with postconditioning, along with better neurologic outcomes. Immunostaining revealed that ischemic postconditioning increased expression of vascular endothelial growth factor (VEGF) in neurons within peri-infarct regions. Correspondingly, we confirmed that VEGFR2 was expressed on Iba1-positive microglia/macrophages, and confocal microscopy showed that in postconditioned rats, these cells were polarized to a ramified morphology with higher expression of M2-like markers. Treating rats with a VEGF receptor 2 kinase inhibitor negated these effects of postconditioning on microglia/macrophage polarization. In vitro, postconditoning after oxygen-glucose deprivation up-regulated VEGF release in primary neuron cultures, and adding VEGF to microglial cultures partly shifted their M2-like markers. Altogether, our findings support the idea that after postconditioning, injured neurons may release VEGF as a 'help-me' signal that promotes microglia/macrophage polarization into potentially beneficial phenotypes.

Indexed as

AnimalsBrain InfarctionBrain IschemiaCalcium-Binding ProteinsCell HypoxiaCell PolarityCells, CulturedDisease Models, AnimalEmbryo, MammalianGlial Fibrillary Acidic ProteinGlucoseInfusions, IntraventricularIschemic PostconditioningMaleMicrofilament ProteinsMicrogliaAif1 protein, ratCalcium-Binding ProteinsGlial Fibrillary Acidic ProteinGlucoseMicrofilament ProteinsReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor Amicroglianeuroprotectionneurovascular unitpostconditioningstroke

Identifiers

PMID29570780
PMCPMC6105375
OpenAlexW2794241261

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.