Evidence map›Paper›PMID 27319402›Full record

ArticleJournal of thrombosis and haemostasis : JTH2016

Physiologic variations in blood plasminogen levels affect outcomes after acute cerebral thromboembolism in mice: a pathophysiologic role for microvascular thrombosis.

S Singh, A K Houng, D Wang, G L Reed

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

S SinghDepartment of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
A K HoungDepartment of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
D WangDepartment of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
G L ReedDepartment of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. glreed@uthsc.edu.
University of Tennessee Health Science Center · US

Funding

Commercialization Readiness Pilot for Amplifying Fibrinolysis in Ischemic StrokeR44NS073147 · NINDS · TRANSLATIONAL SCIENCES, INC. · PI REED, GUY L, WANG, DONG · 2020 to 2021
$3.4M
PLASMINOGEN ACTIVATION &SK: STRUCTURE - FUNCTIONR01HL058496 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI REED, GUY L · 1998 to 2012
$3.3M
Reducing Stroke by a Novel, Clot-dissolving AntibodyU44NS073147 · NINDS · TRANSLATIONAL SCIENCES, INC. · PI KUSSIE, PAUL H, REED, GUY L · 2011 to 2014
$3.3M
Alpha-2-antiplasmin and Ischemic StrokeR01NS089707 · NINDS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI REED, GUY L · 2015 to 2019
$1.9M
Novel Methods for Dissolving Blood ClotsR42HL092750 · NHLBI · TRANSLATIONAL SCIENCES, INC. · PI REED, GUY L · 2012 to 2013
$1.5M
Novel Methods for Dissolving Blood ClotsR44HL092750 · NHLBI · TRANSLATIONAL SCIENCES, INC. · PI KANG, ANDREW H, REED, GUY L · 2015 to 2015
$1.0M
Novel Methods for Dissolving Blood ClotsR41HL092750 · NHLBI · TRANSLATIONAL SCIENCES, INC. · PI REED, GUY L · 2010 to 2010
$168k
NHLBI NIH HHS R01 HL058496NHLBI NIH HHS R41 HL092750NHLBI NIH HHS R42 HL092750NHLBI NIH HHS R44 HL092750NINDS NIH HHS R01 NS089707NINDS NIH HHS R44 NS073147NINDS NIH HHS U44 NS073147
6 · The paper itself

Abstract

unlabelledEssentials Physiologic variations in blood plasminogen (Pg) levels may affect ischemic stroke outcomes. We tested Pg effects in a model with translational relevance to human thromboembolic stroke. A dose-response exists between Pg levels and brain injury, fibrinolysis, barrier breakdown. Higher Pg levels reduce microvascular thrombosis and improve outcomes in ischemic stroke. SUMMARY: Background and Objectives Plasminogen appears to affect brain inflammation, cell movement, fibrinolysis, neuronal excitotoxicity, and cell death. However, brain tissue and circulating blood plasminogen may have different roles, and there is wide individual variation in blood plasminogen levels. The aim of this study was to determine the integrated effect of blood plasminogen levels on ischemic brain injury. Methods We examined thromboembolic stroke in mice with varying, experimentally determined, blood plasminogen levels. Ischemic brain injury, blood-brain barrier breakdown, matrix metalloproteinase-9 expression and microvascular thrombosis were determined. Results Within the range of normal variation, plasminogen levels were strongly associated with ischemic brain injury; higher blood plasminogen levels had dose-related, protective effects. Higher plasminogen levels were associated with increased dissolution of the middle cerebral artery thrombus. Higher plasminogen levels decreased blood-brain barrier breakdown, matrix metalloproteinase-9 expression and microvascular thrombosis in the ischemic brain. In plasminogen-deficient mice, selective restoration of blood plasminogen levels reversed the harmful effects of plasminogen deficiency on ischemic brain injury. Specific inhibition of thrombin also reversed the effect of plasminogen deficiency on ischemic injury by decreasing microvascular thrombosis, blood-brain barrier breakdown, and matrix metalloproteinase-9 expression. Conclusions Variation in blood plasminogen levels, within the range seen in normal individuals, had marked effects on experimental ischemic brain injury. Higher plasminogen levels protected against ischemic brain injury, and decreased blood-brain barrier breakdown, matrix metalloproteinase-9 expression, and microvascular thrombosis. The protective effects of blood plasminogen appear to be mediated largely through a decrease in microvascular thrombosis in the ischemic territory.

Indexed as

Acute DiseaseAnimalsBlood-Brain BarrierBrainBrain InjuriesBrain IschemiaDisease Models, AnimalFemaleHumansIschemiaMaleMatrix Metalloproteinase 9MiceMice, Inbred C57BLMicrocirculationPlasminogenMatrix Metalloproteinase 9Mmp9 protein, mousePlasminogenblood-brain barriercerebral infarctionmatrix metalloproteinase-9plasminogenthromboembolismthrombosis

Identifiers

PMID27319402
PMCPMC5035596
OpenAlexW2468541660

What OpenQuestion holds

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LicenceTDM
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.