We explore cortical microvasculature changes during the progression of atherosclerosis using young and old transgenic atherosclerotic (ATX) mice with thinned-skull cranial window. In awake animals, exploiting intrinsic signal optical imaging, Doppler optical coherence tomography, and two-photon microscopy, we investigate how the progression of atherosclerotic disease affects the morphology and function of cortical microvasculature as well as baseline cerebral tissue oxygenation. Results show that aged ATX mice exhibited weaker hemodynamic response in the somatosensory cortex to whisker stimulation and that the diameter of their descending arterioles and associated mean blood flow decreased significantly compared with the young ATX group. Data from two-photon phosphorescence lifetime microscopy indicate that old ATX mice had lower and more heterogeneous partial pressure of oxygen ( PO 2 ) in cortical tissue than young ATX mice. In addition, hypoxic micropockets in cortical tissue were found in old, but not young, ATX mice. Capillary red blood cell (RBC) flux, RBC velocity, RBC velocity heterogeneity, hematocrit, and diameter were also measured using line scans with two-photon fluorescence microscopy. When compared with the young group, RBC flux, velocity, and hematocrit decreased and RBC velocity heterogeneity increased in old ATX mice, presumably due to disturbed blood supply from arterioles that were affected by atherosclerosis. Finally, dilation of capillaries in old ATX mice was observed, which suggests that capillaries play an active role in compensating for an oxygen deficit in brain tissue.

中文翻译：

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清醒的LDLR-/-hApoB + / +转基因小鼠的动脉粥样硬化疾病对脑微血管和组织氧合的影响。

我们使用薄颅颅窗的年轻和老转基因动脉粥样硬化（ATX）小鼠探索动脉粥样硬化进展过程中的皮质微脉管系统变化。在清醒的动物中，利用内在信号光学成像，多普勒光学相干断层扫描和双光子显微镜，我们研究了动脉粥样硬化疾病的进展如何影响皮层微脉管系统的形态和功能以及基线脑组织氧合。结果表明，与年轻的ATX组相比，衰老的ATX小鼠在体感皮层中对晶须刺激表现出较弱的血液动力学响应，并且降落小动脉的直径和相关的平均血流量显着降低。来自双光子磷光寿命显微镜的数据表明，与年轻的ATX小鼠相比，老年ATX小鼠的皮质组织中的氧分压（PO 2）更低且更高。另外，在老但不年轻的ATX小鼠中发现了皮质组织中的低氧微口袋。毛细血管红细胞通量，RBC速度，RBC速度异质性，血细胞比容和直径也使用双光子荧光显微镜进行线扫描测量。与年轻组相比，老ATX小鼠的RBC通量，速度和血细胞比容降低，RBC速度异质性增加，可能是由于受动脉粥样硬化影响的小动脉血液供应受阻。最后，观察到老ATX小鼠的毛细血管扩张，