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Brezzo, G., Simpson, J. orcid.org/0000-0002-3753-4271, Ameen-Ali, K.E. et al. (2 more authors) (2020) Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function. Brain, Behavior, & Immunity - Health, 5. 100074. ISSN 2666-3546
Abstract
Brain health relies on a tightly regulated system known as neurovascular coupling whereby the cellular constituents of the neuro-glial-vascular unit (NGVU) regulate cerebral haemodynamics in accordance with brain metabolic demand. Disruption of neurovascular coupling impairs brain health and is associated with the development of a number for neurological conditions, including Alzheimer’s disease. The NGVU is also a key site of action for neuroinflammatory responses and contributes to the transition of systemic inflammation to neuroinflammatory processes. Thus, systemic inflammatory challenges may cause a shift in NGVU operation towards prioritising neuroinflammatory action and thus altering neurovascular coupling and resultant cerebrovascular changes. To investigate this, rats were injected with lipopolysaccharide (LPS) (2 mg/kg) to induce a systemic inflammatory response, or vehicle, and brain haemodynamic responses to sensory and non-sensory (hypercapnia) stimuli were assessed in vivo using optical imaging techniques. Following imaging, animals were perfused and their brains extracted to histologically characterise components of the NGVU to determine the association between underlying cellular changes and in vivo blood flow regulation. LPS-treated animals showed changes in haemodynamic function and cerebrovascular dynamics 6 hours after LPS administration. Histological assessment identified a significant increase in astrogliosis, microgliosis and endothelial activation in LPS-treated animals. Our data shows that an acutely induced systemic inflammatory response is able to rapidly alter in vivo haemodynamic function and is associated with significant changes in the cellular constituents of the NGVU. We suggest that these effects are initially mediated by endothelial cells, which are directly exposed to the circulating inflammatory stimulus and have been implicated in regulating functional hyperaemia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | Inflammation; Lipopolysaccharide; Neurovascular coupling; Neuro-glial-vascular unit |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ROYAL SOCIETY UF080113 ROYAL SOCIETY UF130327 WELLCOME TRUST (THE) 093223/B/10/Z MEDICAL RESEARCH COUNCIL MR/M013553/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 May 2020 11:00 |
Last Modified: | 22 Jan 2025 14:14 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.bbih.2020.100074 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:159879 |
Available Versions of this Item
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Acute effects of systemic inflammation upon neurovascular unit and cerebrovascular function. (deposited 22 Jan 2025 14:22)
- Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function. (deposited 06 May 2020 11:00) [Currently Displayed]