Lu Yuankang, Zhang Cong, Lu Xuecong, Moeini Mohammad, Thorin Eric, Lesage Frédéric
École Polytechnique de Montréal, Laboratoire d'Imagerie optique et moléculaire, Montréal, Québec, Canada.
Institut de Cardiologie de Montréal, Montréal, Québec, Canada.
Neurophotonics. 2019 Oct;6(4):045003. doi: 10.1117/1.NPh.6.4.045003. Epub 2019 Oct 24.
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 ( ) 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.
我们使用带有薄颅骨颅窗的年轻和老年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皮质微血管的变化。在清醒动物中，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，我们研究动脉粥样硬化疾病的进展如何影响皮质微血管的形态和功能以及基线脑组织氧合。结果表明，老年ATX小鼠体感皮层对触须刺激的血流动力学反应较弱，与年轻ATX组相比，其下行小动脉直径和相关平均血流量显著降低。双光子磷光寿命显微镜的数据表明，老年ATX小鼠皮质组织中的氧分压（ ）低于年轻ATX小鼠，且更不均匀。此外，在老年而非年轻的ATX小鼠皮质组织中发现了缺氧微区。还使用双光子荧光显微镜的线扫描测量了毛细血管红细胞（RBC）通量、RBC速度、RBC速度异质性、血细胞比容和直径。与年轻组相比，老年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，这可能是由于受动脉粥样硬化影响的小动脉供血紊乱所致。最后，观察到老年ATX小鼠的毛细血管扩张，这表明毛细血管在补偿脑组织氧 deficit 方面发挥了积极作用。
