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

doi:10.1177/0271678X221112278

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 for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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.

Original language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	42
Issue	12
Pages (from-to)	2303-2317
Number of pages	15
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678X221112278
Publication status	Published - Dec 2022

Keywords

Capillary stalling
cerebral microcirculation
hyperaemic response
optical imaging
systemic inflammation

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10.1177/0271678X221112278Licence: CC BY-NC

fruekilde-et-al-2022-disturbed-microcirculation-and-hyperaemic-response-in-a-murine-model-of-systemic-inflammationFinal published version, 1.26 MBLicence: CC BY-NC

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title = "Disturbed microcirculation and hyperaemic response in a murine model of systemic inflammation",

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 {\textquoteleft}capillary stalls{\textquoteright}—a phenomenon previously reported in animal models of stroke and Alzheimer{\textquoteright}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.",

keywords = "Capillary stalling, cerebral microcirculation, hyperaemic response, optical imaging, systemic inflammation",

author = "Fruekilde, {Signe Kirk} and Bailey, {Christopher J.} and Lambertsen, {Kate Lykke} and Clausen, {Bettina Hjelm} and Jasper Carlsen and Xu, {Ning Long} and Drasbek, {Kim Ryun} and Eugenio Guti{\'e}rrez-Jim{\'e}nez",

year = "2022",

month = dec,

doi = "10.1177/0271678X221112278",

language = "English",

volume = "42",

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Disturbed microcirculation and hyperaemic response in a murine model of systemic inflammation. / Fruekilde, Signe Kirk; Bailey, Christopher J.; Lambertsen, Kate Lykke et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 42, No. 12, 12.2022, p. 2303-2317.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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

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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.

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

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