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Original research
Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke
  1. Cyril Dargazanli1,2,
  2. Marine Blaquière2,
  3. Marinette Moynier1,
  4. Frédéric de Bock2,
  5. Julien Labreuche3,
  6. Adrien ter Schiphorst4,
  7. Imad Derraz1,
  8. Răzvan Alexandru Radu1,
  9. Gregory Gascou1,
  10. Pierre Henri Lefevre1,
  11. Francesca Rapido5,
  12. Julien Fendeleur5,
  13. Caroline Arquizan4,
  14. Romain Bourcier6,
  15. Philippe Marin2,
  16. Paolo Machi7,
  17. Federico Cagnazzo1,2,
  18. Christophe Hirtz8,
  19. Vincent Costalat1,2,
  20. Nicola Marchi2
  1. 1Department of Neuroradiology, University Hospital Centre Montpellier, Montpellier, France
  2. 2Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, Montpellier, France
  3. 3Unité Statistique, Évaluation Économique, Data-management, Centre Hospitalier Universitaire de Lille, Lille, France
  4. 4Department of Neurology, CHRU Gui de Chauliac, University Hospital Centre Montpellier, Montpellier, France
  5. 5Department of Anesthesiology and Critical Care Medicine, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France
  6. 6Department of Neuroradiology, Université de Nantes, Nantes, France
  7. 7Department of Neuroradiology, Geneva University Hospitals, Geneve, Switzerland
  8. 8Plateforme Protéomique Clinique, Montpellier, France
  1. Correspondence to Dr Cyril Dargazanli, Department of Neuroradiology, University Hospital Centre Montpellier, Montpellier, Occitanie, France; c-dargazanli{at}chu-montpellier.fr; Dr Nicola Marchi; Nicola.Marchi{at}igf.cnrs.fr; Prof Vincent Costalat; v-costalat{at}chu-montpellier.fr

Abstract

Background Performing endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) allows a port of entry for intracranial biological sampling.

Objective To test the hypothesis that specific immune players are molecular contributors to disease, outcome biomarkers, and potential targets for modifying AIS.

Methods We examined 75 subjects presenting with large vessel occlusion of the anterior circulation and undergoing EVT. Intracranial blood samples were obtained by microcatheter aspiration, as positioned for stent deployment. Peripheral blood samples were collected from the femoral artery. Plasma samples were quality controlled by electrophoresis and analyzed using a Mesoscale multiplex for targeted inflammatory and vascular factors.

Results We measured 37 protein biomarkers in our sample cohort. Through multivariate analysis, adjusted for age, intravenous thrombolysis, pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT scores, we found that post-clot blood levels of interleukin-6 (IL-6) were significantly correlated (adjusted P value <0.05) with disability assessed by the modified Rankin Scale (mRS) score at 90 days, with medium effect size. Chemokine (C-C) ligand 17 CCL17/TARC levels were inversely correlated with the mRS score. Examination of peripheral blood showed that these correlations did not reach statistical significance after correction. Intracranial biomarker IL-6 level was specifically associated with a lower likelihood of favorable outcome, defined as a mRS score of 0–2.

Conclusions Our findings show a signature of blood inflammatory factors at the cerebrovascular occlusion site. The correlations between these acute-stage biomarkers and mRS score outcome support an avenue for add-on and localized immune modulatory strategies in AIS.

  • Thrombectomy
  • Inflammation
  • Stroke
  • Angiography
  • Brain

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • CD, VC and NM contributed equally.

  • Contributors Substantial contributions to the conception or design of the work: CD, MB, NM, JL, VC. Acquisition, analysis, or interpretation of data for the work: all authors. Drafting the work or revising it critically for important intellectual content: CD, NM, JL. Final approval of the version to be published: all authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors. CD, VC, PMac and NM: conception and design of the study, analysis of data, and drafting of the manuscript. MB, FdB, CH, PM: technical analyses of samples. MM: acquisition of patients’ characteristics, registry. CD, VC, MM: patients’ recruitment and approval. CD, VC, ID, RAR, GG, PHL, FR, JF, CA, FC,AtS, RB: samples obtainment and circuit. All authors contributed to the article and approved the submitted version. FC in samples obtainment and circuit. CD is acting as the guarantor.

  • Funding This study was funded by Stryker Neurovascular.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.