Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: A hyperacute role for neutrophils in persistent traffic jams.

Autor:	Erdener ŞE; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA., Tang J; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA., Kılıç K; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA., Postnov D; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark., Giblin JT; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA., Kura S; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA., Chen IA; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA., Vayisoğlu T; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA., Sakadžić S; Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA., Schaffer CB; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA., Boas DA; Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2021 Feb; Vol. 41 (2), pp. 236-252. Date of Electronic Publication: 2020 Apr 01.
DOI:	10.1177/0271678X20914179
Abstrakt:	Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2-24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.
Databáze:	MEDLINE
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