Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke

作者：Christian Staehr, John T. Giblin, Eugenio Gutiérrez‐Jiménez, Halvor Osterby Guldbrandsen, Jianbo Tang, Shaun L. Sandow, David A. Boas, Vladimir V. Matchkov · 发表于：Journal of the American Heart Association · 年份：2023 · DOI：10.1161/jaha.123.029527 · 被引用次数：46 · 研究领域：Thermoregulation and physiological responses、Traumatic Brain Injury and Neurovascular Disturbances、Heart Rate Variability and Autonomic Control

Background 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. Methods and Results 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%] ...