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

Signe Kirk Fruekilde*, Christopher J. Bailey, Kate Lykke Lambertsen, Bettina Hjelm Clausen, Jasper Carlsen, Ning Long Xu, Kim Ryun Drasbek, Eugenio Gutiérrez-Jiménez

*Corresponding author af dette arbejde

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Abstract

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.

OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Vol/bind42
Nummer12
Sider (fra-til)2303-2317
Antal sider15
ISSN0271-678X
DOI
StatusUdgivet - dec. 2022

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