Journal Article Ahead of print 4 citations
PubMed: 42328887 DOI: 10.1002/ana.78284
Hyperacute Interleukin-1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion.
Ann Neurol
Authors: Justine Münsterberg, Caspar Brekenfeld, Hanna Englert, Marius Piepke, Regine J Dress, Martin Oertel, Tina Fischer, Romy Hackbusch, Mingming Zha, Haodi Cai, Christian Casar, Ines S Schädlich, Leo Winter, Alina Jander, Karoline Degenhardt, Maxim Bester, Fabian Flottmann, Uta Hanning, Brigitte Holst, Anna Worthman, Johanna Hiefner, Berenike Rutz, Eckhard Schlemm, Götz Thomalla, Bettina H Clausen, Ann M Stowe, Immo Prinz, Thiruma V Arumugam, Markus Glatzel, Thomas Renné, Jens Fiehler, Eva Tolosa, Tim Magnus, Mathias Gelderblom
Affiliations
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
- Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
- Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia.
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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.
MeSH
Monocytes, Chemokines, Blood, Stroke, Brain, Cerebral Arteries, Neutrophils, Arteries, Cerebrovascular Circulation, Middle Cerebral Artery, Extracellular Traps, Neurology