Vascular pathology is associated with cognitive impairment in diseases such as type 1 diabetes; however, how capillary flow is affected and the underlying mechanisms remain elusive. Here we show that capillaries in the diabetic mouse brain in both sexes are prone to stalling, with blocks consisting primarily of erythrocytes in branches off ascending venules. Screening for circulating inflammatory cytokines revealed persistently high levels of interleukin-10 (IL-10) in diabetic mice. Contrary to expectation, stimulating IL-10 signalling increased capillary obstruction, whereas inhibiting IL-10 receptors with neutralizing antibodies or endothelial specific knockdown in diabetic mice reversed these impairments. Chronic treatment of diabetic mice with IL-10 receptor neutralizing antibodies improved cerebral blood flow, increased capillary flux and diameter, downregulated haemostasis and cell adhesion-related gene expression, and reversed cognitive deficits. These data suggest that IL-10 signalling has an unexpected pathogenic role in cerebral microcirculatory defects and cognitive impairment associated with type 1 diabetes.

血管病理与 1 型糖尿病等疾病的认知障碍有关;然而，毛细血管血流如何受到影响以及潜在机制仍然难以捉摸。在这里，我们表明糖尿病小鼠大脑中的毛细血管在两性中都容易停滞，块主要由升小静脉分支中的红细胞组成。循环炎性细胞因子的筛选显示糖尿病小鼠的白细胞介素 10 （IL-10） 水平持续较高。与预期相反，刺激 IL-10 信号传导会增加毛细血管阻塞，而在糖尿病小鼠中用中和抗体或内皮特异性敲除抑制 IL-10 受体可逆转这些损伤。用 IL-10 受体中和抗体对糖尿病小鼠进行长期治疗可改善脑血流量，增加毛细血管通量和直径，下调止血和细胞粘附相关基因表达，并逆转认知缺陷。这些数据表明，IL-10 信号传导在与 1 型糖尿病相关的脑微循环缺陷和认知障碍中具有意想不到的致病作用。