Evidence map›Paper›PMID 29890880›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019

Urokinase-type plasminogen activator (uPA) protects the tripartite synapse in the ischemic brain via ezrin-mediated formation of peripheral astrocytic processes.

Ariel Diaz, Paola Merino, Luis G Manrique, Lihong Cheng, Manuel Yepes

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.7field-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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Plasminogen activator inhibitor-1 mediates cerebral ischemia-induced astrocytic reactivity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Article
  7. Article
  8. The uPA/uPAR system in astrocytic wound healing.Neural regeneration research · 2022
    Review
  9. Article
  10. Tissue-type plasminogen activator induces TNF-α-mediated preconditioning of the blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  11. Review
  12. Review
  13. Urokinase-type plasminogen activator promotes N-cadherin-mediated synaptic recovery in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Article
  14. Article
  15. Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021
    Review
  16. Article
  17. Urokinase-Type Plasminogen Activator Protects Cerebral Cortical Neurons from Soluble Aβ-Induced Synaptic Damage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  18. Review
  19. Observational
  20. 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 1 institution in 1 country.

Ariel DiazDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Paola MerinoDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Luis G ManriqueDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Lihong ChengDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Manuel YepesDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.ORCID 0000-0002-5224-9663
Emory University · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Urokinase-type Plasminogen Activator in the Ischemic BrainR01NS091201 · NINDS · EMORY UNIVERSITY · PI YEPES, MANUEL SALVADOR · 2015 to 2022
$2.7M
tPA is a Neuroprotectant in the Ischemic BrainR01NS079331 · NINDS · EMORY UNIVERSITY · PI YEPES, MANUEL SALVADOR · 2013 to 2017
$1.7M
TPA Protects the Synapse in the Iscemic BrainI01BX003441 · VA · VETERANS HEALTH ADMINISTRATION · PI YEPES, MANUEL SALVADOR · 2017 to 2025
–
BLRD VA I01 BX003441NIH HHS P51 OD011132NINDS NIH HHS R01 NS079331NINDS NIH HHS R01 NS091201
6 · The paper itself

Abstract

Cerebral ischemia has a harmful effect on the synapse associated with neurological impairment. The "tripartite synapse" is assembled by the pre- and postsynaptic terminals, embraced by astrocytic elongations known as peripheral astrocytic processes (PAPs). Ischemic stroke induces the detachment of PAPs from the synapse, leading to synaptic dysfunction and neuronal death. Ezrin is a membrane-associated protein, required for the formation of PAPs, that links the cell surface to the actin cytoskeleton. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to its receptor (uPAR) promotes neurite growth during development. In the adult brain, neurons release uPA and astrocytes recruit uPAR to the plasma membrane during the recovery phase from an ischemic stroke, and uPA/uPAR binding promotes functional improvement following an ischemic injury. We found that uPA induces the synthesis of ezrin in astrocytes, with the subsequent formation of PAPs that enter in direct contact with the synapse. Furthermore, either the release of neuronal uPA or intravenous treatment with recombinant uPA (ruPA) induces the formation of PAPs in the ischemic brain, and the interaction of these PAPs with the pre- and postsynaptic terminals protects the integrity of the "tripartite synapse" from the harmful effects of the ischemic injury.

Indexed as

AstrocytesBrain IschemiaCells, CulturedCytoskeletal ProteinsEzrinHumansNeuronsReceptors, Urokinase Plasminogen ActivatorSynapsesUrokinase-Type Plasminogen ActivatorZinc FingersCytoskeletal ProteinsEzrinReceptors, Urokinase Plasminogen ActivatorUrokinase-Type Plasminogen ActivatorezrinneurorepairPeripheral astrocytic processesplasminurokinase-type plasminogen activator

Identifiers

PMID29890880
PMCPMC6827113
OpenAlexW2808227038

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.