Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O₂ is critical in brain physiology, tissue O₂ level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO₂) in the deep WM. We tested this hypothesis by monitoring WM tissue pO₂ using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO₂ from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO₂ to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO₂ was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO₂ may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO₂ in the WM of small animals.