Neutrophils Obstructing Brain Capillaries Are a Major Cause of No-Reflow in Ischemic Stroke.
- El Amki M Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Glück C Experimental Imaging and Neuroenergetics, Institute of Pharmacology and Toxicology, University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Binder N Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Middleham W Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Wyss MT Experimental Imaging and Neuroenergetics, Institute of Pharmacology and Toxicology, University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Weiss T Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Meister H Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Luft A Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Weller M Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland.
- Weber B Experimental Imaging and Neuroenergetics, Institute of Pharmacology and Toxicology, University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland. Electronic address: bweber@pharma.uzh.ch.
- Wegener S Department of Neurology, University Hospital and University of Zurich, and Zurich Neuroscience Center, Zurich, Switzerland. Electronic address: susanne.wegener@usz.ch.
- 2020-10-14
Published in:
- Cell reports. - 2020
English
Despite successful clot retrieval in large vessel occlusion stroke, ∼50% of patients have an unfavorable clinical outcome. The mechanisms underlying this functional reperfusion failure remain unknown, and therapeutic options are lacking. In the thrombin-model of middle cerebral artery (MCA) stroke in mice, we show that, despite successful thrombolytic recanalization of the proximal MCA, cortical blood flow does not fully recover. Using in vivo two-photon imaging, we demonstrate that this is due to microvascular obstruction of ∼20%-30% of capillaries in the infarct core and penumbra by neutrophils adhering to distal capillary segments. Depletion of circulating neutrophils using an anti-Ly6G antibody restores microvascular perfusion without increasing the rate of hemorrhagic complications. Strikingly, infarct size and functional deficits are smaller in mice treated with anti-Ly6G. Thus, we propose neutrophil stalling of brain capillaries to contribute to reperfusion failure, which offers promising therapeutic avenues for ischemic stroke.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.celrep.2020.108260
- PMID 33053341
- Persistent URL
- https://folia.unifr.ch/global/documents/169344
Statistics
Document views: 14
File downloads:
- fulltext.pdf: 0