Xanthine oxidase mediates chronic stress-induced cerebrovascular dysfunction and cognitive impairment

• Published in: Journal of cerebral blood flow and metabolism 2023-06, Vol.43 (6), p.905-920
• Main Authors: Burrage, Emily N, Coblentz, Tyler, Prabhu, Saina S, Childers, Ryan, Bryner, Randy W, Lewis, Sarah E, DeVallance, Evan, Kelley, Eric E, Chantler, Paul D
• Format: Article
• Language: English
• Subjects: Animals; Cardiovascular Physiological Phenomena - drug effects; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cerebrovascular Disorders - drug therapy; Cerebrovascular Disorders - etiology; Cerebrovascular Disorders - psychology; Cognitive Dysfunction - enzymology; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Enzyme Inhibitors - pharmacology; Febuxostat - pharmacology; Free Radicals - metabolism; Hydrogen Peroxide; Memory, Short-Term - drug effects; Memory, Short-Term - physiology; Mice; Mice, Inbred C57BL; Original; Stress, Psychological - enzymology; Stress, Psychological - metabolism; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X231152551

Xanthine oxidase (XO) mediates vascular function. Chronic stress impairs cerebrovascular function and increases the risk of stroke and cognitive decline. Our study determined the role of XO on stress-induced cerebrovascular dysfunction and cognitive decline. We measured middle cerebral artery (MCA) function, free radical formation, and working memory in 6-month-old C57BL/6 mice who underwent 8 weeks of control conditions or unpredictable chronic mild stress (UCMS) with or without febuxostat (50 mg/L), a XO inhibitor. UCMS mice had an impaired MCA dilation to acetylcholine vs. controls (p