Erdener Şefik E, Tang Jianbo, Kılıç Kıvılcım, Postnov Dmitry, Giblin John T, Kura Sreekanth, Chen I-Chun A, Vayisoğlu Tuğberk, Sakadžić Sava, Schaffer Chris B, Boas David A
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.
J Cereb Blood Flow Metab. 2021 Feb;41(2):236-252. doi: 10.1177/0271678X20914179. Epub 2020 Apr 1.
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.
自从引入溶栓治疗以及随后急性缺血性卒中血管内治疗的扩展以来，尽管实现了再通，但实际疗效仍不尽人意，其原因尚待明确。在此，通过对小鼠毛细血管循环进行高时空分辨率成像，我们发现了脑毛细血管中动态血流停滞的病理现象，这种现象在再灌注后可挽救的半暗带中持续存在。这些停滞不同于无再流的永久性细胞阻塞，它们在毛细血管网络中临时且反复出现，像小范围的局部交通堵塞一样损害整体循环。缺血半暗带的体内显微镜检查显示，白细胞在毛细血管腔内缓慢移动或滞留，而在再灌注条件下，相邻节段的红细胞流动受到干扰。通过注射特异性靶向中性粒细胞的抗Ly6G抗体，可以调节停滞动态。停滞数量和持续时间的减少与再灌注后2至24小时内半暗带血流的改善相关，同时毛细血管氧合增加、细胞损伤减少且功能结局改善。因此，动态微循环停滞现象可能是半暗带持续损伤的一个促成因素，并且是一种潜在的超急性机制，补充了先前关于活化中性粒细胞在缺血性卒中中的有害作用的观察结果。
