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Disturbed microcirculation and hyperaemic response in a murine model of systemic inflammation

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  • Signe Kirk Fruekilde, University of Chinese Academy of Sciences
  • ,
  • Christopher J. Bailey, University of Chinese Academy of Sciences
  • ,
  • Kate Lykke Lambertsen, Syddansk Universitet
  • ,
  • Bettina Hjelm Clausen, Syddansk Universitet
  • ,
  • Jasper Carlsen
  • Ning Long Xu, University of Chinese Academy of Sciences, Chinese Academy of Sciences
  • ,
  • Kim Ryun Drasbek
  • Eugenio Gutiérrez-Jiménez

Systemic inflammation affects cognitive functions and increases the risk of dementia. This phenomenon is thought to be mediated in part by cytokines that promote neuronal survival, but the continuous exposure to which may lead to neurodegeneration. The effects of systemic inflammation on cerebral blood vessels, and their provision of adequate oxygen to support critical brain parenchymal cell functions, remains unclear. Here, we demonstrate that neurovascular coupling is profoundly disturbed in lipopolysaccharide (LPS) induced systemic inflammation in awake mice. In the 24 hours following LPS injection, the hyperaemic response of pial vessels to functional activation was attenuated and delayed. Concurrently, under steady-state conditions, the capillary network displayed a significant increase in the number of capillaries with blocked blood flow, as well as increased duration of ‘capillary stalls’—a phenomenon previously reported in animal models of stroke and Alzheimer’s disease pathology. We speculate that vascular changes and impaired oxygen availability may affect brain functions following acute systemic inflammation and contribute to the long-term risk of neurodegenerative changes associated with chronic, systemic inflammation.

TidsskriftJournal of Cerebral Blood Flow and Metabolism
Sider (fra-til)2303-2317
Antal sider15
StatusUdgivet - dec. 2022

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