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Updated: May 2, 2026

A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia
Published on: September 16, 2017
Tissue oxygen is reduced in white matter of spontaneously hypertensive-stroke prone rats: a longitudinal study with
John Weaver1, Fakhreya Y Jalal2, Yi Yang3
1Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
Abstract:
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.
Insights
Small vessel disease impacts white matter (WM) in vascular cognitive impairment (VCI). This study monitored WM oxygen levels in a rat model, finding a significant decrease correlating with WM damage.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Physiology
Background:
- Small vessel disease is linked to white matter hyperintensities (WMHs) in vascular cognitive impairment (VCI).
- White matter (WM) is susceptible to hypoxic-ischemic injury, yet in vivo oxygen levels in WM remain understudied.
- Understanding WM oxygen dynamics is crucial for VCI research.
Purpose of the Study:
- To investigate the hypothesis that white matter (WM) tissue oxygen (pO₂) decreases in a rat model of vascular cognitive impairment (VCI).
- To monitor changes in WM pO₂ using electron paramagnetic resonance (EPR) oximetry.
- To explore the relationship between WM pO₂ and white matter damage.
Main Methods:
- Utilized spontaneously hypertensive stroke-prone rats (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO) to model VCI.
- Employed in vivo electron paramagnetic resonance (EPR) oximetry to continuously monitor white matter (WM) tissue pO₂.
- Observed rats over several weeks before and after the JPD/UCAO intervention.
Main Results:
- White matter (WM) tissue pO₂ initially increased by up to 32% between 9 and 12 weeks.
- Following JPD/UCAO, WM pO₂ dramatically decreased to near hypoxic levels from weeks 13 to 16.
- This reduction in pO₂ was concurrent with observed white matter damage and microvascular hemorrhages.
Conclusions:
- Alterations in white matter (WM) tissue oxygen (pO₂) may play a role in the development of WM damage in this vascular cognitive impairment (VCI) rat model.
- Electron paramagnetic resonance (EPR) oximetry is a viable method for monitoring brain pO₂ in the white matter of small animals.
- These findings provide insights into the pathophysiology of VCI and potential therapeutic targets.
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