Sato Yoshimichi, Kato Yuya, Kanoke Atsushi, Sun Jennifer Y, Nishijima Yasuo, Wang Ruikang K, Stryker Michael, Endo Hidenori, Liu Jialing
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
SFVAMC, San Francisco, CA, USA.
J Cereb Blood Flow Metab. 2025 May 29:271678X251338203. doi: 10.1177/0271678X251338203.
Type 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel diameter changes in pial arteries and veins and leukocyte-endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice, T2DM mice already exhibited smaller pial vessels with reduced flow velocity prior to stroke. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in inflammation and chronic remodeling of leptomeningeal vessels may contribute to the observed hemodynamics deficiency after stroke and subsequent poor stroke outcome.
2型糖尿病（T2DM）与软脑膜侧支循环代偿受损及卒中预后不良相关。卒中后中性粒细胞在内皮细胞上的黏附和滚动也可独立降低血流速度。然而，T2DM患者侧支循环的时间顺序和拓扑变化尚未明确。在此，我们使用双光子显微镜在清醒的对照小鼠和T2DM小鼠中描述了大脑中动脉（MCA）卒中后软脑膜动脉和静脉的空间和时间血流动力学、血管直径变化以及白细胞-内皮细胞黏附情况。与对照小鼠相比，T2DM小鼠在卒中前就已表现出软脑膜血管较小且血流速度降低。卒中后，T2DM小鼠软脑膜动脉和静脉中的血流持续减少，导致下游穿通动脉血流恢复不良以及微血管血流持续不足。与对照小鼠相比，T2DM小鼠卒中后静脉内皮细胞上的白细胞黏附也持续增加，同时脑实质中的中性粒细胞浸润增加。我们的数据表明，T2DM诱导的炎症增加和软脑膜血管的慢性重塑可能导致卒中后观察到的血流动力学缺陷以及随后的不良卒中预后。
