Abstract
Chronic atherosclerosis may cause cerebral hypoperfusion and inadequate brain oxygenation, contributing to the progression of cognitive decline. In this study, we exploited two-photon phosphorescence lifetime microscopy to measure the absolute partial pressure of oxygen (PO2) in cortical tissue in both young and old LDLR-/-, hApoB100+/+ mice, spontaneously developing atherosclerosis with age. Capillary red-blood-cell (RBC) speed, flux, hematocrit and capillary diameter were also measured by two-photon imaging of FITC-labelled blood plasma. Our results show positive correlations between RBC speed, flux, diameter and capillary-adjacent tissue PO2. When compared to the young mice, we observed lower tissue PO2, lower RBC speed and flux, and smaller capillary diameter in the old atherosclerotic mice. The old mice also exhibited a higher spatial heterogeneity of tissue PO2, and RBC speed and flux, suggesting a less efficient oxygen extraction.
Highlights
Chronic atherosclerosis has a lifelong impact on brain health [1,2,3,4,5,6,7,8,9]
The role of capillaries in oxygen delivery was emphasized in several modeling studies showing that brain tissue oxygenation benefits from the increase in absolute capillary blood flow and from its homogenization [19,20,21]
Performing the same measures in an older group, we studied age-related differences in cortical tissue PO2, capillary RBC speed and flux, the degree of capillary blood flow heterogeneity, and capillary diameter
Summary
Chronic atherosclerosis has a lifelong impact on brain health [1,2,3,4,5,6,7,8,9]. It can cause cerebral hypoperfusion and cerebrovascular disorders [10,11,12], which, in turn, impairs normal cognitive function [12,13,14,15]. The recent synthesis of an oxygen-sensitive phosphorescence probe PtP-C343, which can be combined with two-photon phosphorescence lifetime microscopy, enabled measurements of the absolute partial pressure of oxygen (PO2) in the parenchymal tissue of brain at the micron scale [22,23,24]. Exploiting this key development, we aim here to experimentally characterize the distribution of brain tissue oxygenation and cortical capillary blood flow, as well as to investigate the relation between capillary blood flow homogenization and brain tissue oxygenation, in a mouse model of atherosclerosis. Performing the same measures in an older group, we studied age-related differences in cortical tissue PO2, capillary RBC speed and flux, the degree of capillary blood flow heterogeneity, and capillary diameter
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