Evidence map›Paper›PMID 26961944›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016

Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke.

David Fernández-López, Joel Faustino, Alexander L Klibanov, Nikita Derugin, Elodie Blanchard, Franziska Simon, Stephen L Leib, Zinaida S Vexler

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 4% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Csf1Experimental biology and medicine (Maywood, N.J.) · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  18. Article
  19. Cerebral ischemia in the developing brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Review
  20. Article

7 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

8 authors at 3 institutions in 2 countries.

David Fernández-LópezDepartment of Neurology, University of California-San Francisco, San Francisco, California 94158.
Joel FaustinoDepartment of Neurology, University of California-San Francisco, San Francisco, California 94158.
Alexander L KlibanovDepartment of Medicine, University of Virginia, Charlottesville, Virginia 22908, and.
Nikita DeruginDepartment of Neurology, University of California-San Francisco, San Francisco, California 94158.
Elodie BlanchardDepartment of Neurology, University of California-San Francisco, San Francisco, California 94158.
Franziska SimonInstitute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland.
Stephen L LeibInstitute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland.ORCID http://orcid.org/0000-0002-1106-6123
Zinaida S VexlerDepartment of Neurology, University of California-San Francisco, San Francisco, California 94158, Zena.Vexler@ucsf.edu.
University of California, San Francisco · USUniversity of Bern · CHUniversity of Virginia · US

Funding

Neonatal Stroke: The Role of Microglia-derived Extracellular VesiclesR01NS044025 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VEXLER, ZINAIDA S · 2002 to 2023
$7.7M
Macrophages as modulators of repair after neonatal strokeR01NS076726 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VEXLER, ZINAIDA S · 2012 to 2016
$1.8M
CINC-1 as a modulator of blood-brain barrier integrity after neonatal strokeR01NS055915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VEXLER, ZINAIDA S · 2009 to 2010
$775k
Blood-brain barrier function after neonatal and pediatric experimental strokeR21NS080015 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VEXLER, ZINAIDA S · 2012 to 2013
$445k
NINDS NIH HHS R01 NS044025NINDS NIH HHS R01 NS055915NINDS NIH HHS R01 NS076726NINDS NIH HHS R01 NS44025NINDS NIH HHS R01 NS55915NINDS NIH HHS R01 NS76726NINDS NIH HHS R21 NS080015
6 · The paper itself

Abstract

Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral artery occlusion (tMCAO). Microglial depletion by intracerebral injection of liposome-encapsulated clodronate at P5 significantly reduced vessel coverage and triggered hemorrhages in injured regions 24 h after tMCAO. Lack of microglia did not alter expression or intracellular redistribution of several tight junction proteins, did not affect degradation of collagen IV induced by the tMCAO, but altered cell types producing TGFβ1 and the phosphorylation and intracellular distribution of SMAD2/3. Selective inhibition of TGFbr2/ALK5 signaling in microglia via intracerebral liposome-encapsulated SB-431542 delivery triggered hemorrhages after tMCAO, demonstrating that TGFβ1/TGFbr2/ALK5 signaling in microglia protects from hemorrhages. Consistent with observations in neonatal rats, depletion of microglia before tMCAO in P9 Cx3cr1(GFP/+)/Ccr2(RFP/+) mice exacerbated injury and induced hemorrhages at 24 h. The effects were independent of infiltration of Ccr2(RFP/+) monocytes into injured regions. Cumulatively, in two species, we show that microglial cells protect neonatal brain from hemorrhage after acute ischemic stroke.

Indexed as

Age FactorsAnimalsAnimals, NewbornBenzamidesBone Density Conservation AgentsCaspase 3Clodronic AcidDioxolesDisease Models, AnimalEndothelial CellsFemaleGene Expression Regulation, DevelopmentalInfarction, Middle Cerebral ArteryIntracranial HemorrhagesMaleMice4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideBenzamidesBone Density Conservation AgentsCaspase 3Clodronic AcidDioxolesSmad2 ProteinTransforming Growth Factor beta1blood–brain barrierextracellular matrixinflammationmiddle cerebral artery occlusionpostnatalTGFβ1

Identifiers

PMID26961944
PMCPMC4783493
OpenAlexW2296454444

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.