Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function

Brezzo, G., Simpson, J., Ameen-Ali, K. , Berwick, J. and Martin, C. (2020) Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function. Brain, Behavior, and Immunity: Health, 5, 100074. (doi: 10.1016/j.bbih.2020.100074)

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) (2mg/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 six 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.

• Item Type: Articles
• Additional Information: This study was supported by The Royal Society [CM, UF130327]; the Wellcome Trust [CM, WT093223AIA]; the Medical Research Council [CM & JB, MR/M013553/1]; Alzheimer’s Research UK [JB, KA-A, IRG2014-10] and The University of Sheffield [GB, PhD Teaching Fellowship].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Brezzo, Dr Gaia and Ameen-Ali, Dr Kamar
• Authors: Brezzo, G., Simpson, J., Ameen-Ali, K., Berwick, J., and Martin, C.
• Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Brain, Behavior, and Immunity: Health
• Publisher: Elsevier
• ISSN: 2666-3546
• ISSN (Online): 2666-3546
• Published Online: 22 April 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Brain, Behavior, and Immunity: Health 5:100074
• Publisher Policy: Reproduced under a Creative Commons license