Binder, Nadine Felizitas; El Amki, Mohamad; Glück, Chaim; Middleham, William; Reuss, Anna Maria; Bertolo, Adrien; Thurner, Patrick; Deffieux, Thomas; Lambride, Chryso; Epp, Robert; Handelsmann, Hannah-Lea; Baumgartner, Philipp; Orset, Cyrille; Bethge, Philipp; Kulcsar, Zsolt; Aguzzi, Adriano; Tanter, Mickael; Schmid, Franca; Vivien, Denis; Wyss, Matthias Tasso; ... (2024). Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization. Neuron, 112(9), 1456-1472.e6. Elsevier 10.1016/j.neuron.2024.01.031
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research |
UniBE Contributor: |
Lambride, Chryso |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1097-4199 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
04 Mar 2024 13:48 |
Last Modified: |
04 May 2024 00:14 |
Publisher DOI: |
10.1016/j.neuron.2024.01.031 |
PubMed ID: |
38412858 |
Uncontrolled Keywords: |
in vivo imaging ischemic stroke leptomeningeal collaterals recanalization reperfusion injury stroke patients thrombolysis vascular reactivity |
BORIS DOI: |
10.48350/193536 |
URI: |
https://boris.unibe.ch/id/eprint/193536 |
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