Evidence map›Paper›PMID 39499487›Full record

ArticleTranslational stroke research2025

Blockade of the Platelet-Driven CXCL7-CXCR1/2 Inflammatory Axis Prevents Murine Cerebral Aneurysm Formation and Rupture.

Kamil W Nowicki, Aditya Mittal, Joseph S Hudson, Michael P D'Angelo, Michael M McDowell, Catherine Cao, Rohit Mantena, Abhishek Jauhari, Robert M Friedlander

Abstract read
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In one paragraph

Article in Translational stroke research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. A Future Blood Test to Detect Cerebral Aneurysms.Cellular and molecular neurobiology · 2023
    Review
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

9 authors.

Kamil W NowickiDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA. kn2675@cumc.columbia.edu.
Aditya MittalDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Joseph S HudsonDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Michael P D'AngeloDepartment of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Michael M McDowellDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Catherine CaoDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Rohit MantenaDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Abhishek JauhariDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
Robert M FriedlanderDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Platelet aggregation is intimately associated with vascular inflammation and is commonly seen on routine histology studies of cerebral aneurysms. Platelets, when activated, have been shown to augment neutrophil response and the pro-inflammatory cascade. Platelet-neutrophil complexes have been found to aggravate atherosclerosis through a positive feedback loop. We hypothesized that targeting platelet aggregation and downstream inflammation could be used to prevent aneurysm formation and progression. First, we induced cerebral aneurysm formation in a previously described intracranial aneurysm model via carotid artery ligation, hypertension, and stereotactic elastase injection in C57BL/6 mice and analyzed vessels for lesion and thrombus formation. Raybiotech cytokine arrays were used to analyze 96 cytokines in induced murine aneurysms and 120 cytokines in human tissue samples. Cerebral aneurysm formation and inflammatory pathway were then studied in animals treated with IgG2 antibody (control), anti-GpIb antibody (platelet depletion), 1:10 DMSO:PBS (control), clopidogrel, anti-CXCR1/2 small molecule inhibitor, or anti-CXCL7 antibody. Bleeding assays and flow cytometry were used to evaluate platelet function in treated groups. CD31 + platelet aggregates are a common feature in human and mouse cerebral aneurysm specimens. Platelet ablation in mice prevents cerebral aneurysm formation (20% vs 100% in control antibody-treated mice, n = 5 each, p = 0.0476). Mice treated with 1 mg/kg clopidogrel develop significantly less aneurysms than controls (18% vs 73%, n = 11 and 11, respectively, p = 0.03). Semi-quantitative analysis of 96 different cytokines using Raybiotech arrays shows increased protein expression of CXCL7 in murine cerebral aneurysms when compared to controls. Treatment with clopidogrel results in reciprocal decrease in detected CXCL7. Targeting CXCL7-CXCR1/2 axis with 10 mg/kg reparixin (CXCR1/2 antagonist) significantly decreases cerebral aneurysm formation (11% vs 73%, n = 9 and 11, p = 0.0098) while treatment with 10 mg/kg SB225002 tends to decrease aneurysm formation (36% vs 73%, n = 11 vs n = 7, p = 0.11). Lastly, specific antibody blockade against CXCL7 using anti-CXCL7 antibody at 100 ug/mL significantly decreases cerebral aneurysm formation (29% vs 75%, n = 7 vs n = 8, p = 0.046). Platelet inflammation has an important role in cerebral aneurysm formation. Small molecule inhibitors targeting platelet CXCL7-CXCR1/2 inflammatory axis could be used to prevent cerebral aneurysm formation or progression.

Indexed as

Aneurysm, RupturedBlood PlateletsIntracranial AneurysmReceptors, Interleukin-8BAnimalsClopidogrelDisease Models, AnimalHumansInflammationMaleMiceMice, Inbred C57BLPlatelet AggregationPlatelet Aggregation InhibitorsReceptors, CXCRClopidogrelCmkor1 protein, mouseCxcr2 protein, mousePlatelet Aggregation InhibitorsReceptors, CXCRReceptors, Interleukin-8BAneurysmCerebralCXCL7CXCR1/2InflammationMurinePlatelet

Identifiers

PMID39499487

What OpenQuestion holds

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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.