Neutrophil granulocytes promote flow stagnation due to dynamic capillary stalls following experimental stroke

活体显微镜检查 缺血 转基因小鼠 大脑中动脉 渗透(HVAC) 病理 脑缺血 闭塞 体内 医学 内皮干细胞 粒细胞 内科学 免疫学 转基因 心脏病学 炎症 冲程(发动机) 生物 微循环 体外 材料科学 物理 复合材料 生物技术 基因 热力学 生物化学
作者
Leoni Rolfes,Monika Riek‐Burchardt,Marc Pawlitzki,Jens Minnerup,Stefanie Böck,Mariella Schmidt,Sven G. Meuth,Matthias Gunzer,Jens Neumann
出处
期刊:Brain Behavior and Immunity [Elsevier BV]
卷期号:93: 322-330 被引量:27
标识
DOI:10.1016/j.bbi.2021.01.011
摘要

Flow stagnation of peri-ischemic capillaries due to dynamic leukocyte stalls has been described to be a contributor to ongoing penumbral injury in transient brain ischemia, but has not been investigated in permanent experimental stroke so far. Moreover, it is discussed that obstructing neutrophils are involved in this process; however, their contribution has not yet been proven. Here, we characterize the dynamics of neutrophil granulocytes in two models of permanent stroke (photothrombosis and permanent middle cerebral artery occlusion) using intravital two-photon fluorescence microscopy. Different to previous studies on LysM-eGFP+ cells we additionally apply a transgenic mouse model with tdTomato-expressing neutrophils to avoid interference from additional immune cell subsets. We identify repetitively occurring capillary stalls of varying duration promoted by neutrophils in both models of permanent cerebral ischemia, validating the suitability of our new transgenic mouse model in determining neutrophil occlusion formation in vivo. Flow cytometric analysis of peripheral blood (PB) and brain tissue from mice subjected to photothrombosis reveal an increase in the total proportion of neutrophils, with selective upregulation of endothelial adherence markers in the PB. In conclusion, the dynamic microcirculatory stall phenomenon that is described after transient ischemia followed by reperfusion also occurs after permanent small- or large-vessel stroke and is clearly attributable to neutrophils.
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