Impact of atherosclerotic disease on cerebral microvasculature and tissue oxygenation in awake LDLR−/−hApoB+/+ transgenic mice

Abstract

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.

Cerebral tissue pO2 response to treadmill exercise in awake mice

“…The observation that cerebral tissue is more oxygenated at exercise levels of 5-15 m/min suggests beneficial effects of exercise in situations that oxygen delivery to the brain is compromised, such as in aging 9 , atherosclerosis [36][37][38] , hypertension 39 and Alzheimer Disease (AD) 40 . Although very short-term effects of acute exercise were investigated in this study, but it is expected that routine long-term exercise could improve cerebral oxygenation and function in above conditions.…”