Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

in vivo imaging ischemic stroke leptomeningeal collaterals recanalization reperfusion injury stroke patients thrombolysis vascular reactivity

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
16 Feb 2024
Historique:
received: 03 05 2023
revised: 18 11 2023
accepted: 30 01 2024
medline: 28 2 2024
pubmed: 28 2 2024
entrez: 27 2 2024
Statut: aheadofprint

Résumé

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Identifiants

DOI: 10.1016/j.neuron.2024.01.031 PMID: 38412858
pubmed: 38412858
pii: S0896-6273(24)00057-6
doi: 10.1016/j.neuron.2024.01.031
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Nadine Felizitas Binder (NF)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Mohamad El Amki (M)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Chaim Glück (C)

Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

William Middleham (W)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Anna Maria Reuss (AM)

Institute of Neuropathology, University Hospital Zurich, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Adrien Bertolo (A)

Iconeus, 6 rue Jean Calvin, Paris, France; Physics for Medicine, INSERM U1273, ESPCI Paris, CNRS UMR 8063, PSL Research University, 17 rue Moreau, Paris, France.

Patrick Thurner (P)

Department of Neuroradiology, University Hospital and University of Zurich, Zürich, France.

Thomas Deffieux (T)

Physics for Medicine, INSERM U1273, ESPCI Paris, CNRS UMR 8063, PSL Research University, 17 rue Moreau, Paris, France.

Chryso Lambride (C)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Robert Epp (R)

Institute of Fluid Dynamics, ETH Zurich, Zurich, Switzerland.

Hannah-Lea Handelsmann (HL)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland.

Philipp Baumgartner (P)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland.

Cyrille Orset (C)

Normandie University, UNICAEN, INSERM, Unité Mixte de Recherche-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen Normandie, GIP Cyceron, Caen, France.

Philipp Bethge (P)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Zsolt Kulcsar (Z)

Department of Neuroradiology, University Hospital and University of Zurich, Zürich, France.

Adriano Aguzzi (A)

Institute of Neuropathology, University Hospital Zurich, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Mickael Tanter (M)

Physics for Medicine, INSERM U1273, ESPCI Paris, CNRS UMR 8063, PSL Research University, 17 rue Moreau, Paris, France.

Franca Schmid (F)

ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.

Denis Vivien (D)

Normandie University, UNICAEN, INSERM, Unité Mixte de Recherche-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen Normandie, GIP Cyceron, Caen, France; Department of Clinical Research, Caen Normandie University Hospital, Caen, France.

Matthias Tasso Wyss (MT)

Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Andreas Luft (A)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Michael Weller (M)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Bruno Weber (B)

Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.

Susanne Wegener (S)

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland. Electronic address: susanne.wegener@usz.ch.

Classifications MeSH