Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: A hyperacute role for neutrophils in persistent traffic jams
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Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury : A hyperacute role for neutrophils in persistent traffic jams. / Erdener, Sefik E.; Tang, Jianbo; Kilic, Kivilcim; Postnov, Dmitry; Giblin, John T.; Kura, Sreekanth; Chen, I-Chun A.; Vayisoglu, Tugberk; Sakadzic, Sava; Schaffer, Chris B.; Boas, David A.
I: Journal of Cerebral Blood Flow and Metabolism, Bind 41, Nr. 2, 2021, s. 236–252.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury
T2 - A hyperacute role for neutrophils in persistent traffic jams
AU - Erdener, Sefik E.
AU - Tang, Jianbo
AU - Kilic, Kivilcim
AU - Postnov, Dmitry
AU - Giblin, John T.
AU - Kura, Sreekanth
AU - Chen, I-Chun A.
AU - Vayisoglu, Tugberk
AU - Sakadzic, Sava
AU - Schaffer, Chris B.
AU - Boas, David A.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Cerebral ischemia
KW - capillary
KW - microcirculation
KW - neutrophil
KW - stall
KW - CEREBRAL-ARTERY OCCLUSION
KW - SELECTIVE NEURONAL LOSS
KW - PROVIDES NEUROPROTECTION
KW - STROKE
KW - BRAIN
KW - MOUSE
KW - PERFUSION
KW - ADHESION
KW - MODELS
KW - DEPOLARIZATIONS
U2 - 10.1177/0271678X20914179
DO - 10.1177/0271678X20914179
M3 - Journal article
C2 - 32237951
VL - 41
SP - 236
EP - 252
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 2
ER -
ID: 247336796