Evidence map›Paper›PMID 27586239›Full record

ArticleJournal of neuroinflammation2016

Cerebral ischemia-induced angiogenesis is dependent on tumor necrosis factor receptor 1-mediated upregulation of α5β1 and αVβ3 integrins.

Heng Huang, Qijuan Huang, Fuxin Wang, Richard Milner, Longxuan Li

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Targeting Neurovascular Pathways: Gene Therapy as a Novel Treatment for Vascular Dementia After Stroke.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Angiogenesis after ischemic stroke.Acta pharmacologica Sinica · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Inflammation-Mediated Angiogenesis in Ischemic Stroke.Frontiers in cellular neuroscience · 2021
    Review
  12. Article
  13. Article
  14. Angiogenesis in the ischemic core: A potential treatment target?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Review
  15. Review
  16. 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

5 authors at 2 institutions in 2 countries.

Heng HuangDepartment of Neurology, Guangdong Medical University Affiliated Hospital, Zhanjiang, 524001, People's Republic of China.
Qijuan HuangDepartment of Neurology, Guangdong Medical University Affiliated Hospital, Zhanjiang, 524001, People's Republic of China.
Fuxin WangDepartment of Neurology, Guangdong Medical University Affiliated Hospital, Zhanjiang, 524001, People's Republic of China.
Richard MilnerDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. rmilner@scripps.edu.
Longxuan LiDepartment of Neurology, Gongli Hospital, 219 Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. Longxuanlee2006@yahoo.com.
Guangdong Medical College · CNScripps Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), is expressed in ischemic tissue and is known to modulate angiogenesis; however, the role of the two distinct TNF-α receptors, TNFR1 and TNFR2, in mediating angiogenic signaling after cerebral ischemic stroke is relatively unknown.

methodsC57BL6 mice were subject to 90 min of ischemia by temporary occlusion of the middle cerebral artery (MCAO) and given daily intra-cerebroventricular injections of antibodies against TNFR1, TNFR2 or control IgG (doses of 10, 50, and 100 ng/day) for 4 days following 90 min MCAO. Vascular remodeling and α5β1 and αVβ3 integrin expression were then examined in the brains of these mice after 4, 7, and 14 days post-ischemia. In parallel in vitro studies, flow cytometry was used to determine the influence of TNF-α on proliferation and integrin expression of human brain microvascular endothelial cells (HBMECs).

resultsThe post-ischemic cerebral angiogenic response was inhibited by antibodies against TNFR1 but not TNFR2, and this correlated with reduced endothelial proliferation and decreased α5β1 and αVβ3 integrin expression after 4 and 7 days post-ischemia. Consistent with these findings, in vitro studies showed that TNF-α induced endothelial proliferation and upregulation of α5β1 and αVβ3 integrins was abrogated by anti-TNFR1 but not anti-TNFR2 antibodies in cultured HBMECs. In addition, blocking antibodies to α5β1 and αVβ3 integrins significantly inhibited TNF-α-induced HBMEC proliferation.

conclusionsOur results suggest that TNFR1-mediated signaling plays a critical role in triggering angiogenic integrins and subsequent angiogenic responses following cerebral ischemia. These novel findings could form a platform for future therapeutic strategies aimed at stimulating angiogenesis following cerebral ischemia.

Indexed as

AnimalsAntibodiesBrainCell ProliferationCells, CulturedCytokinesDisease Models, AnimalEndothelial CellsHumansInfarction, Middle Cerebral ArteryIntegrin alpha5beta1Integrin alphaVbeta3MaleMiceMice, Inbred C57BLNeovascularization, PathologicAntibodiesCytokinesIntegrin alpha5beta1Integrin alphaVbeta3Receptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIAngiogenesisCerebral ischemiaIntegrinTumor necrosis factor-α

Identifiers

PMID27586239
PMCPMC5009537
OpenAlexW2515865543

What OpenQuestion holds

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LicenceCC BY
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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.