Evidence map›Paper›PMID 36727508›Full record

ArticleStroke2023

Rapid Activation of Neuroinflammation in Stroke: Plasma and Extracellular Vesicles Obtained on a Mobile Stroke Unit.

Robert G Kowalski, Aurélie Ledreux, John E Violette, Robert T Neumann, David Ornelas, Xiaoli Yu, Steven G Griffiths, Scott Lewis, Priscilla Nash, Andrew A Monte and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 3 pooled it
4.4field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 37 citations in OpenAlex.

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  11. Circulating Interleukin-6 Levels and Timing of Acute Ischemic Stroke Onset.Annals of clinical and translational neurology · 2025
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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

15 authors at 8 institutions in 3 countries.

Robert G KowalskiDepartment of Neurosurgery (R.G.K., A.L., R.T.N., X.Y., M.W.G.).ORCID 0000-0002-6043-3671
Aurélie LedreuxDepartment of Neurosurgery (R.G.K., A.L., R.T.N., X.Y., M.W.G.).ORCID 0000-0001-6232-7672
John E VioletteUCHealth, University of Colorado Hospital, Aurora (J.E.V., D.O.).ORCID 0000-0002-9658-3583
Robert T NeumannDepartment of Neurosurgery (R.G.K., A.L., R.T.N., X.Y., M.W.G.).
David OrnelasUCHealth, University of Colorado Hospital, Aurora (J.E.V., D.O.).ORCID 0000-0002-2307-1739
Xiaoli YuDepartment of Neurosurgery (R.G.K., A.L., R.T.N., X.Y., M.W.G.).ORCID 0000-0003-4850-8586
Steven G GriffithsX0S0ME, Moncton, New Brunswick, Canada (S.G.G.).
Scott LewisVivitide, Gardner, MA (S.L.).ORCID 0000-0003-1817-6031
Priscilla NashRegis University, Denver, CO (P.N.).ORCID 0000-0002-0152-3925
Andrew A MonteDepartment of Emergency Medicine (A.A.M.).ORCID 0000-0002-6210-8418
Christina M CoughlanDepartment of Neurology (RGK, CMC, WJJ).
Clayton DeighanNanoView Biosciences, Boston, MA (C.D.).
James C GrottaMemorial Hermann Hospital-Texas Medical Center, Houston (J.C.G.).ORCID 0000-0002-3667-4248
William J JonesDepartment of Neurology (RGK, CMC, WJJ).ORCID 0000-0002-6383-2598
Michael W GranerDepartment of Neurosurgery (R.G.K., A.L., R.T.N., X.Y., M.W.G.).
University of Colorado Denver · USUniversity of Colorado Hospital · USClayton Foundation · CHMemorial Hermann · USNeumann University · USRegis University · USTwitter (United States) · USUniversité de Moncton · CA

Funding

PERSONALIZING EMERGENCY/ACUTE THERAPEUTICS UTILIZING SYSTEMS BIOLOGY (PEGASUS)R35GM124939 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MONTE, ANDREW ALBERT · 2017 to 2021
$2.1M
NIGMS NIH HHS R35 GM124939NINDS NIH HHS L30 NS124052
6 · The paper itself

Abstract

backgroundNeuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit.

methodsThe study is a proof-of-concept, cohort investigation of ultra-early blood- and extracellular vesicle-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained, prehospital, on an mobile stroke unit. Outcomes were biomarker concentrations, modified Rankin Scale score, and National Institutes of Health Stroke Scale score.

resultsForty-one adults were analyzed, including 15 patients treated on the mobile stroke unit between August 2021 and April 2022, and 26 healthy controls to establish biomarker reference levels. Median patient age was 74 (range, 36-97) years, 60% were female, and 80% White. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely transient ischemic attack or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial National Institutes of Health Stroke Scale score was 11 (range, 4-19) and 6 (75%) received tPA (tissue-type plasminogen activator). Blood was obtained a median of 58 (range, 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma IL-6 (interleukin-6), neurofilament light chain, UCH-L1 (ubiquitin C-terminal hydrolase L1), and GFAP (glial fibrillary acidic protein) were elevated by as much as 10 times normal. In EVs, MMP-9 (matrix metalloproteinase-9), CXCL4 (chemokine (C-X-C motif) ligand 4), CRP (C-reactive protein), IL-6, OPN (osteopontin), and PECAM1 (platelet and endothelial cell adhesion molecule 1) were elevated. Inflammatory markers increased rapidly in the first 2 hours and continued rising for 24 hours.

conclusionsThe neuroinflammatory cascade was found to be activated within 36 to 133 minutes after stroke and progresses rapidly. This is earlier than observed previously in humans and suggests injury from neuroinflammation occurs faster than had been surmised. These findings could inform development of acute immunomodulatory stroke therapies and lead to new diagnostic tools and improved outcomes.

Indexed as

Brain IschemiaIschemic Attack, TransientStrokeAdultAgedAged, 80 and overFemaleHumansInterleukin-6MaleMiddle AgedNeuroinflammatory DiseasesTissue Plasminogen ActivatorTreatment OutcomeInterleukin-6Tissue Plasminogen Activatoradultbiomarkerfemaleinterventionsneuroinflammatory diseases

Identifiers

PMID36727508
PMCPMC10052772
OpenAlexW4318913464

What OpenQuestion holds

Textmetadata
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.