血管可塑性的窗口与中风后行为恢复相关联。

A Window of Vascular Plasticity Coupled to Behavioral Recovery after Stroke.

机构信息

Institute for Neuroscience

Department of Psychology.

出版信息

J Neurosci. 2020 Sep 30;40(40):7651-7667. doi: 10.1523/JNEUROSCI.1464-20.2020. Epub 2020 Sep 1.

Abstract

Stroke causes remodeling of vasculature surrounding the infarct, but whether and how vascular remodeling contributes to recovery are unclear. We established an approach to monitor and compare changes in vascular structure and blood flow with high spatiotemporal precision after photothrombotic infarcts in motor cortex using longitudinal 2-photon and multiexposure speckle imaging in mice of both sexes. A spatially graded pattern of vascular structural remodeling in peri-infarct cortex unfolded over the first 2 weeks after stroke, characterized by vessel loss and formation, and selective stabilization of a subset of new vessels. This vascular structural plasticity was coincident with transient activation of transcriptional programs relevant for vascular remodeling, reestablishment of peri-infarct blood flow, and large improvements in motor performance. Local vascular plasticity was strongly predictive of restoration of blood flow, which was in turn predictive of behavioral recovery. These findings reveal the spatiotemporal evolution of vascular remodeling after stroke and demonstrate that a window of heightened vascular plasticity is coupled to the reestablishment of blood flow and behavioral recovery. Our findings support that neovascularization contributes to behavioral recovery after stroke by restoring blood flow to peri-infarct regions. These findings may inform strategies for enhancing recovery from stroke and other types of brain injury. An improved understanding of neural repair could inform strategies for enhancing recovery from stroke and other types of brain injury. Stroke causes remodeling of vasculature surrounding the lesion, but whether and how the process of vascular remodeling contributes to recovery of behavioral function have been unclear. Here we used longitudinal imaging to track vascular structure and blood flow in residual peri-infarct cortex after ischemic stroke in mice. We found that stroke created a restricted period of heightened vascular plasticity that was associated with restoration of blood flow, which was in turn predictive of recovery of motor function. Therefore, our findings support that vascular remodeling facilitates behavioral recovery after stroke by restoring blood flow to peri-infarct cortex.

摘要

中风会导致梗塞周围的血管结构发生重塑,但血管重塑是否以及如何有助于功能恢复尚不清楚。我们建立了一种方法,通过在雄性和雌性小鼠的皮质光血栓性梗塞后使用纵向双光子和多曝光散斑成像,以高时空精度监测和比较梗塞周围皮质血管结构和血流的变化。梗塞周围皮质的血管结构重塑呈现空间梯度模式,在中风后前 2 周内展开,表现为血管损失和形成,以及一小部分新血管的选择性稳定。这种血管结构可塑性与与血管重塑、梗塞周围血流重建以及运动功能的显著改善相关的转录程序的短暂激活同时发生。局部血管可塑性与血流恢复的恢复高度相关,而血流恢复又与行为恢复相关。这些发现揭示了中风后血管重塑的时空演变,并表明血管可塑性增强的窗口与血流恢复和行为恢复相关。我们的发现支持血管新生通过恢复梗塞周围区域的血流有助于中风后的行为恢复。这些发现可能为增强中风和其他类型的脑损伤的恢复提供策略。对神经修复的深入了解可以为增强中风和其他类型的脑损伤的恢复提供策略。中风会导致病变周围的血管结构发生重塑,但血管重塑过程是否以及如何有助于行为功能的恢复一直不清楚。在这里,我们使用纵向成像技术在缺血性中风后的小鼠中追踪梗塞周围残留皮质的血管结构和血流。我们发现中风产生了一个受限的血管重塑增强期,与血流恢复相关,而血流恢复又与运动功能的恢复相关。因此,我们的发现支持血管重塑通过恢复梗塞周围皮质的血流促进中风后的行为恢复。

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