Hypertension accelerates cerebral tissue PO₂ disruption in Alzheimer's disease

This study measured stimulus-evoked brain tissue oxygenation changes in a mouse model of Alzheimer disease (AD) and further explored the influence of exercise and angiotensin II-induced hypertension on these changes. in vivo two-photon phosphorescence lifetime microscopy was used to investigate local changes in brain tissue oxygenation following whisker stimulation. During rest periods, PO₂ values close to the arteriolar wall were lower in the AD groups and the PO₂ spatial decay as a function of distance to arteriole was increased by hypertension. During stimulation, tissue PO₂ response had a similar spatial dependence across groups. Tissue PO₂ response in post-stimulation period was larger in AD groups (e.g., AD6 and ADH6) than in the controls (WT6 and WTH6). After a 3-month voluntary exercise period, some of these changes were reversed in AD mice. This provides novel insight into tissue oxygen delivery and the impact of blood pressure control and exercise on brain tissue oxygenation in AD.