Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer's disease.
Chang LiuAlfredo Cárdenas-RiveraShayna TeitelbaumAustin BirminghamMohammed AlfadhelMohammad A YaseenPublished in: bioRxiv : the preprint server for biology (2023)
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. 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 lipopolysaccaride-induced neuroinflammation. 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. This study provides evidence that neuroinflammation alters cerebral oxygen demand at the early stages of AD without substantially altering vascular oxygen supply. The results will guide our understanding of neuroinflammation's influence on neuroimaging biomarkers for early AD diagnosis.
Keyphrases
- red blood cell
- cerebral ischemia
- lipopolysaccharide induced
- lps induced
- cognitive impairment
- traumatic brain injury
- mouse model
- subarachnoid hemorrhage
- wild type
- inflammatory response
- brain injury
- blood brain barrier
- coronary artery
- high fat diet induced
- diabetic rats
- skeletal muscle
- single molecule
- optical coherence tomography
- functional connectivity
- stress induced