Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA.
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA.
Cell Rep. 2021 Oct 5;37(1):109794. doi: 10.1016/j.celrep.2021.109794.
Cortical spreading depolarizations (CSDs) are increasingly suspected to play an exacerbating role in a range of acute brain injuries, including stroke, possibly through their interactions with cortical blood flow. We use simultaneous wide-field imaging of neural activity and hemodynamics in Thy1-GCaMP6f mice to explore the neurovascular dynamics of CSDs during and following Rose Bengal-mediated photothrombosis. CSDs are observed in all mice as slow-moving waves of GCaMP fluorescence extending far beyond the photothrombotic area. Initial CSDs are accompanied by profound vasoconstriction and leave residual oligemia and ischemia in their wake. Later, CSDs evoke variable responses, from constriction to biphasic to vasodilation. However, CSD-evoked vasoconstriction is found to be more likely during rapid, high-amplitude CSDs in regions with stronger oligemia and ischemia, which, in turn, worsens after each repeated CSD. This feedback loop may explain the variable but potentially devastating effects of CSDs in the context of acute brain injury.
皮层扩散性去极化(CSD)被越来越多地怀疑在一系列急性脑损伤中起恶化作用,包括中风,可能是通过它们与皮质血流的相互作用。我们使用 Thy1-GCaMP6f 小鼠中的神经活动和血液动力学的同时宽场成像来探索 Rose Bengal 介导的光血栓形成过程中和之后 CSD 的神经血管动力学。CSD 在所有小鼠中都被观察到,是缓慢移动的 GCaMP 荧光波,延伸范围远远超出光血栓形成区域。最初的 CSD 伴随着明显的血管收缩,并在其后面留下残余的低氧血症和缺血。后来,CSD 引起的反应从收缩到双相再到血管扩张各不相同。然而,在具有更强的低氧血症和缺血的区域中,快速、高幅度的 CSD 中更可能发生 CSD 引起的血管收缩,这反过来又在每次重复 CSD 后恶化。这种反馈环可能解释了 CSD 在急性脑损伤背景下的可变但潜在破坏性影响。