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, Luft Andreas, Weller Michael, Weber Bruno, Wegener Susanne
Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.
Neuron. 2024 May 1;112(9):1456-1472.e6. doi: 10.1016/j.neuron.2024.01.031. Epub 2024 Feb 26.
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.
血管再通是缺血性中风治疗的主要手段。然而，即使能及时清除血栓，许多中风患者的恢复情况仍很差。软脑膜侧支循环（LMCs）是具有尚未明确功能的软膜吻合血管。我们在基于凝血酶的中风和纤溶治疗小鼠模型中应用激光散斑成像、超快超声和双光子显微镜，以表明LMCs维持脑自动调节并允许逐渐再灌注，从而导致小梗死灶。在LMCs较差的小鼠中，远端动脉段塌陷，有害的充血会导致再通后出血和死亡。计算机分析证实了LMCs对维持缺血区域灌注的相关性。因此，在接受血栓切除术且侧支循环较差的中风患者中，快速再灌注会导致出血性转化和不良恢复。因此，我们将LMCs确定为调节再灌注和预防中风后无效再通的关键组成部分。未来的治疗干预应旨在增强侧支循环功能，使中风后实现有益的再灌注。
