S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Rosanna Rossi; Andrew Douglas; Sara Molina Gil; Duaa Jabrah; Abhay Pandit; Michael Gilvarry; Ray McCarthy; James Prendergast; Katarina Jood; Petra Redfors; Annika Nordanstig; Erik Ceder; Dennis Dunker; Jeanette Carlqvist; István Szikora; John Thornton; Georgios Tsivgoulis; Klearchos Psychogios; Turgut Tatlisumak; Alexandros Rentzos; Karen M Doyle

doi:10.3389/fneur.2022.1067215

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Front Neurol. 2023 Jan 23:13:1067215. doi: 10.3389/fneur.2022.1067215. eCollection 2022.

Authors

Rosanna Rossi^{1

2}, Andrew Douglas^{1

2}, Sara Molina Gil^{1

2}, Duaa Jabrah¹, Abhay Pandit², Michael Gilvarry³, Ray McCarthy³, James Prendergast¹, Katarina Jood^{4

5}, Petra Redfors^{4

5}, Annika Nordanstig^{4

5}, Erik Ceder⁶, Dennis Dunker⁶, Jeanette Carlqvist⁶, István Szikora⁷, John Thornton⁸, Georgios Tsivgoulis⁹, Klearchos Psychogios¹⁰, Turgut Tatlisumak^{4

5}, Alexandros Rentzos⁶, Karen M Doyle^{1

2}

Affiliations

¹ Department of Physiology and Galway Neuroscience Centre, School of Medicine, National University of Ireland, Galway, Ireland.
² CÚRAM-SFI Research Centre in Medical Devices, National University of Ireland Galway, Galway, Ireland.
³ Cerenovus, Galway, Ireland.
⁴ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁵ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Interventional and Diagnostic Neuroradiology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Neurointerventions, National Institute of Clinical Neurosciences, Budapest, Hungary.
⁸ Department of Radiology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
⁹ Second Department of Neurology, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
¹⁰ Stroke Unit, Metropolitan Hospital, Piraeus, Greece.

Abstract

Background and purpose: Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.

Methods: We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.

Results: PTIH was associated with higher S100b levels in clots (0.33 [0.08-0.85] vs. 0.07 [0.02-0.27] mm², H1 = 6.021, P = 0.014^*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0-23.0] vs. 14.0 [10.5-19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1-4] vs. 1 [1-2.5], H1 = 5.995, P = 0.014^*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.

Conclusions: Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.

Keywords: S100b; acute ischemic stroke; post-thrombectomy intracranial hemorrhages; stroke biomarkers; thrombus.

Copyright © 2023 Rossi, Douglas, Gil, Jabrah, Pandit, Gilvarry, McCarthy, Prendergast, Jood, Redfors, Nordanstig, Ceder, Dunker, Carlqvist, Szikora, Thornton, Tsivgoulis, Psychogios, Tatlisumak, Rentzos and Doyle.

Grants and funding

This publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant No. 13/RC/2073_2. Furthermore, the authors declare that this study received funding from Cerenovus. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.