title: Tissue oxygen is reduced in white matter of spontaneously hypertensive-stroke prone rats: a longitudinal study with electron paramagnetic resonance.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: John
authors.initials: J
authors.lastname: Weaver
authors.affiliation: 1] Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA [2] Departments of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE.
authors.forename: Fakhreya Y
authors.initials: FY
authors.lastname: Jalal
authors.affiliation: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thompson
authors.affiliation: 1] Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA [2] Department of Neuroscience, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA [3] Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rosenberg
authors.affiliation: 1] Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA [2] Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Ke J
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D010100:Oxygen