Evidence map›Paper›PMID 26337969›Full record

ArticleStroke2015

Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice.

Josephine Herz, Pascal Sabellek, Thomas E Lane, Matthias Gunzer, Dirk M Hermann, Thorsten R Doeppner

Open access · bronzeAbstract read
In one paragraph

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 2% 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

128 citing papers in PubMed, 1 synthesis or guideline pooled it, 208 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. Cytoprotection Concepts for Ischemic Stroke in the Recanalization Era.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  10. Article
  11. A Composite Model - "VASS-DCI" - for Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: Role of VASOGRADE and Inflammatory Biomarkers.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2025
    Article
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68 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

6 authors at 1 institution in 2 countries.

Josephine HerzFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.). josephine.herz@uk-essen.de thorsten.doeppner@uk-essen.de.
Pascal SabellekFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.).
Thomas E LaneFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.).
Matthias GunzerFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.).
Dirk M HermannFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.).
Thorsten R DoeppnerFrom the Department of Neurology (J.H., P.S., D.M.H., T.R.D.), Department of Pediatrics I (J.H.), and Institute of Experimental Immunology and Imaging, University Duisburg-Essen (M.G.), University Hospital Essen, Essen, Germany; and Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City (T.E.L.).
University of Utah · US

Funding

Chemokines and Viral-Induced Neurologic DiseaseR01NS041249 · NINDS · UNIVERSITY OF UTAH · PI LANE, THOMAS E · 2002 to 2019
$5.4M
NINDS NIH HHS R01 NS041249NINDS NIH HHS R01NS041249
6 · The paper itself

Abstract

background and purposeInflammation-related comorbidities contribute to stroke-induced immune responses and brain damage. We previously showed that hyperlipidemia exacerbates ischemic brain injury, which is associated with elevated peripheral and cerebral granulocyte numbers. Herein, we evaluate the contribution of neutrophils to the exacerbation of ischemic brain injury.

methodsWild-type mice fed with a normal chow and ApoE knockout mice fed with a high cholesterol diet were exposed to middle cerebral artery occlusion. CXCR2 was blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. Neutrophils were depleted using an anti-Ly6G antibody. At 72 hours post ischemia, immunohistochemistry, flow cytometry, and real-time polymerase chain reaction were performed to determine cerebral tissue injury and immunologic changes in the blood, bone marrow, and brain. Functional outcome was assessed by accelerated rota rod and tight rope tests at 4, 7, and 14 days post ischemia.

resultsCXCR2 antagonization reduced neurological deficits and infarct volumes that were exacerbated in hyperlipidemic ApoE-/- mice. This effect was mimicked by neutrophil depletion. Cerebral neutrophil infiltration and peripheral neutrophilia, which were increased on ischemia in hyperlipidemia, were attenuated by CXCR2 antagonization. This downscaling of neutrophil responses was associated with increased neutrophil apoptosis and reduced levels of CXCR2, inducible nitric oxide synthase, and NADPH oxidase 2 expression on bone marrow neutrophils.

conclusionsOur data demonstrate a role of neutrophils in the exacerbation of ischemic brain injury induced by hyperlipidemia. Accordingly, CXCR2 blockade, which prevents neutrophil recruitment into the brain, might be an effective option for stroke treatment in patients with hyperlipidemia.

Indexed as

AnimalsApolipoproteins EBrain IschemiaCholesterol, DietaryFlow CytometryGene Expression ProfilingHyperlipidemiasImmunohistochemistryInfarction, Middle Cerebral ArteryInflammationMembrane GlycoproteinsMiceMice, KnockoutNADPH Oxidase 2NADPH OxidasesNeutrophilsApolipoproteins ECholesterol, DietaryCybb protein, mouseMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNitric Oxide Synthase Type IINos2 protein, mousePhenylurea CompoundsReceptors, Interleukin-8BRNA, MessengerSB 225002brain injuryCXCR2hyperlipidemiainflammationneutrophilsstroke

Identifiers

PMID26337969
PMCPMC4589522
OpenAlexW2137358434

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.