Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke.
Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke.
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缺血性卒中后，神经血管解耦与缺血性核心外区域微循环功能障碍有关。
DOI：
10.1161/jaha.123.029527
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发表时间：
2023-06-06
影响因子：
5.4
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中科院分区：
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正常的脑功能取决于血管系统增加血液流向高代谢需求区域的能力。神经血管耦合受损，如局部充血反应神经元活动，可能导致中风后神经预后不良，尽管成功的再通，即无效的再通。在实验前，对植入慢性颅窗的小鼠进行清醒头固定训练。用单血管光血栓术诱导大脑前中动脉闭塞1小时。通过光学相干断层扫描和激光散斑造影评估脑灌注和神经血管耦合。通过标记凝集素和血小板衍生生长因子受体β，研究了灌注固定组织中的毛细血管和周细胞。动脉闭塞在1小时内引起多次扩张性去极化，与缺血周围皮层血流显著减少有关。在3小时和24小时的随访中，大约一半的缺血周围毛细血管不再灌注（分别减少45% [95% CI， 33%-58%]和53% [95% CI， 39%-66%]； P<0.0001），这与同等比例的缺血周围毛细血管周细胞收缩有关。缺血周围皮层毛细血管保持灌注时，动态血流失速的点发生率增加（基线时为0.5% [95% CI, 0.2%-0.7%]，随访3小时和24小时分别为5.1% [95% CI, 3.2% [1.1%-5.3%]， P=0.001）。与基线时观察到的结果相比，在3小时和24小时的随访中，须刺激导致感觉皮层中对应于缺血周围区域的神经血管耦合反应减少。动脉闭塞导致缺血周围皮层毛细血管周细胞收缩和毛细血管流动停滞。毛细血管功能障碍与神经血管解耦有关。与毛细血管功能障碍相关的神经血管偶联损伤可能是导致无效再通的机制之一。因此，本研究的结果为改善脑卒中后神经系统预后提供了新的治疗靶点。
Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Mice implanted with chronic cranial windows were trained for awake head‐fixation before experiments. One‐hour occlusion of the anterior middle cerebral artery branch was induced using single‐vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion‐fixed tissue by labeling lectin and platelet‐derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri‐ischemic cortex. Approximately half of the capillaries in the peri‐ischemic area were no longer perfused at the 3‐ and 24‐hour follow‐up (45% [95% CI, 33%–58%] and 53% [95% CI, 39%–66%] reduction, respectively; P<0.0001), which was associated with contraction of an equivalent proportion of peri‐ischemic capillary pericytes. The capillaries in the peri‐ischemic cortex that remained perfused showed increased point prevalence of dynamic flow stalling (0.5% [95% CI, 0.2%–0.7%] at baseline, 5.1% [95% CI, 3.2%–6.5%] and 3.2% [95% CI, 1.1%–5.3%] at 3‐ and 24‐hour follow‐up, respectively; P=0.001). Whisker stimulation at the 3‐ and 24‐hour follow‐up led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri‐ischemic region compared with that observed at baseline. Arterial occlusion led to contraction of capillary pericytes and capillary flow stalling in the peri‐ischemic cortex. Capillary dysfunction was associated with neurovascular uncoupling. Neurovascular coupling impairment associated with capillary dysfunction may be a mechanism that contributes to futile recanalization. Hence, the results from this study suggest a novel treatment target to improve neurological outcome after stroke.