Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer’s disease

作者：Chang Liu, Alfredo Cárdenas‐Rivera, Shayna Teitelbaum, Austin Birmingham, Mohammed Alfadhel, Mohammad A. Yaseen · 发表于：Alzheimer s Research & Therapy · 年份：2024 · DOI：10.1186/s13195-024-01444-5 · 被引用次数：14 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Neurological Disease Mechanisms and Treatments

BACKGROUND: Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer's disease (AD). Numerous studies have asserted a close association between neuroinflammation and disrupted cerebral energetics. During AD progression and other neurodegenerative disorders, a persistent state of chronic neuroinflammation reportedly exacerbates cytotoxicity and potentiates neuronal death. Here, we assessed the impact of a neuroinflammatory challenge on metabolic demand and microvascular hemodynamics in the somatosensory cortex of an AD mouse model. METHODS: We utilized in vivo 2-photon microscopy and the phosphorescent oxygen sensor Oxyphor 2P to measure partial pressure of oxygen (pO2) and capillary red blood cell flux in cortical microvessels of awake mice. Intravascular pO2 and capillary RBC flux measurements were performed in 8-month-old APPswe/PS1dE9 mice and wildtype littermates on days 0, 7, and 14 of a 14-day period of lipopolysaccharide-induced neuroinflammation. RESULTS: Before the induced inflammatory challenge, AD mice demonstrated reduced metabolic demand but similar capillary red blood cell flux as their wild type counterparts. Neuroinflammation provoked significant reductions in cerebral intravascular oxygen levels and elevated oxygen extraction in both animal groups, without significantly altering red blood cell flux in capillaries. CONCLUSIONS: This study provides evidence that neuroinflammation alters cerebral oxygen ...