Hyperacute Interleukin-1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion

Authors

• Justine Münsterberg, University of Hamburg
• Caspar Brekenfeld, University of Hamburg
• Hanna Englert, University of Hamburg
• Marius Piepke, University of Hamburg
• Regine J. Dress, University of Hamburg
• Martin Oertel, University of Hamburg
• Tina Fischer, University of Hamburg
• Romy Hackbusch, University of Hamburg
• Mingming Zha, University of Hamburg
• Haodi Cai, University of Hamburg
• Christian Casar, University of Hamburg
• Ines S. Schädlich, University of Hamburg
• Leo Winter, University of Hamburg
• Alina Jander, University of Hamburg
• Karoline Degenhardt, University of Hamburg
• Maxim Bester, University of Hamburg
• Fabian Flottmann, University of Hamburg
• Uta Hanning, University of Hamburg
• Brigitte Holst, University of Hamburg
• Anna Worthman, University of Hamburg
• Johanna Hiefner, University of Hamburg
• Berenike Rutz, University of Hamburg
• Eckhard Schlemm, University of Hamburg
• Götz Thomalla, University of Hamburg
• Bettina H. Clausen, University of Southern Denmark
• Ann M. Stowe, University of KentuckyFollow
• Immo Prinz, University of Hamburg
• Thiruma V. Arumugam, La Trobe University
• Markus Glatzel, University of Hamburg
• Thomas Renné, University of Hamburg
• Jens Fiehler, University of Hamburg
• Eva Tolosa, University of Hamburg

Abstract

Objective: Cerebral ischemia remains a major cause of disability, and the contribution of the hyperacute immune response is increasingly recognized. The aim of this study was to investigate the local inflammatory response in the affected brain of stroke patients with large vessel occlusion during the hyperacute phase of stroke. Methods: To decipher the role of myeloid immune cells in stroke-induced inflammation, we performed an unsupervised multiomics analysis of innate immune pathways in ischemic blood obtained directly from the occluded middle cerebral artery in 54 patients undergoing mechanical recanalization. Paired nonischemic arterial blood served as an internal control. Results: Stroke triggered a local hyperacute activation of classical monocytes and neutrophils in the ischemic cerebral vasculature, with interleukin (IL)-1β emerging as a key mediator of inflammation. Elevated plasma adenosine triphosphate levels and inflammasome priming in intravascular monocytes were associated with IL-1β production within the occluded middle cerebral artery within 4.5 hours of stroke onset. IL-1β release coincided with increased neutrophil-attracting chemokines (C-X-C motif chemokine ligand 1 [CXCL1], IL-8). Locally activated neutrophils formed neutrophil extracellular traps (NETs) within the ischemic vasculature, a hallmark of thromboinflammation. Postmortem analyses revealed NET deposition within ischemic brain parenchyma. Interpretation: These findings indicate increased IL-1β expression and enhanced NET formation within the cerebral circulation in stroke caused by large vessel occlusion, suggesting that these mechanisms might contribute to early stroke pathophysiology and represent potential targets for immunomodulatory strategies. ANN NEUROL 2026.

Document Type

Article

Publication Date

1-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Digital Object Identifier (DOI)

10.1002/ana.78284

Archival?

Archival

Repository Citation

Münsterberg, Justine; Brekenfeld, Caspar; Englert, Hanna; Piepke, Marius; Dress, Regine J.; Oertel, Martin; Fischer, Tina; Hackbusch, Romy; Zha, Mingming; Cai, Haodi; Casar, Christian; Schädlich, Ines S.; Winter, Leo; Jander, Alina; Degenhardt, Karoline; Bester, Maxim; Flottmann, Fabian; Hanning, Uta; Holst, Brigitte; Worthman, Anna; Hiefner, Johanna; Rutz, Berenike; Schlemm, Eckhard; Thomalla, Götz; Clausen, Bettina H.; Stowe, Ann M.; Prinz, Immo; Arumugam, Thiruma V.; Glatzel, Markus; Renné, Thomas; Fiehler, Jens; and Tolosa, Eva, "Hyperacute Interleukin-1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion" (2026). Neurology Faculty Publications. 156.
https://uknowledge.uky.edu/neurology_facpub/156