TY - JOUR
T1 - Disturbed microcirculation and hyperaemic response in a murine model of systemic inflammation
AU - Fruekilde, Signe Kirk
AU - Bailey, Christopher J.
AU - Lambertsen, Kate Lykke
AU - Clausen, Bettina Hjelm
AU - Carlsen, Jasper
AU - Xu, Ning Long
AU - Drasbek, Kim Ryun
AU - Gutiérrez-Jiménez, Eugenio
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Capillary stalling
KW - cerebral microcirculation
KW - hyperaemic response
KW - optical imaging
KW - systemic inflammation
UR - http://www.scopus.com/inward/record.url?scp=85137023446&partnerID=8YFLogxK
U2 - 10.1177/0271678X221112278
DO - 10.1177/0271678X221112278
M3 - Journal article
C2 - 35999817
AN - SCOPUS:85137023446
SN - 0271-678X
VL - 42
SP - 2303
EP - 2317
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 12
ER -