The blood-brain barrier in systemic inflammation
The blood-brain barrier in systemic inflammation
The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how this may affect CNS function in health and disease. We first describe the structure and function of the BBB, and outline the techniques used to study the BBB in vitro, and in animal and human settings. We then summarise the evidence from a range of models linking BBB changes with systemic inflammation, and the underlying mechanisms. The clinical relevance of these BBB changes during systemic inflammation are discussed in the context of clinically-apparent syndromes such as sickness behaviour, delirium, and septic encephalopathy, as well as neurological conditions such as Alzheimer’s disease and multiple sclerosis. We review emerging evidence for two novel concepts: (1) a heightened sensitivity of the diseased, versus healthy, BBB to systemic inflammation, and (2) the contribution of BBB changes induced by systemic inflammation to progression of the primary disease process.
blood-brain barrier, systemic inflammation, lipopolysaccharide, sickness behaviour, delirium, septic encephalopathy, multiple sclerosis, alzheimer’s disease
1-12
Varatharaj, Aravinthan
33d833af-9459-4b21-8489-ce9c0b6a09e0
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
February 2017
Varatharaj, Aravinthan
33d833af-9459-4b21-8489-ce9c0b6a09e0
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Abstract
The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how this may affect CNS function in health and disease. We first describe the structure and function of the BBB, and outline the techniques used to study the BBB in vitro, and in animal and human settings. We then summarise the evidence from a range of models linking BBB changes with systemic inflammation, and the underlying mechanisms. The clinical relevance of these BBB changes during systemic inflammation are discussed in the context of clinically-apparent syndromes such as sickness behaviour, delirium, and septic encephalopathy, as well as neurological conditions such as Alzheimer’s disease and multiple sclerosis. We review emerging evidence for two novel concepts: (1) a heightened sensitivity of the diseased, versus healthy, BBB to systemic inflammation, and (2) the contribution of BBB changes induced by systemic inflammation to progression of the primary disease process.
Text
Varatharaj Galea 2017
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More information
Accepted/In Press date: 15 March 2016
e-pub ahead of print date: 16 March 2016
Published date: February 2017
Keywords:
blood-brain barrier, systemic inflammation, lipopolysaccharide, sickness behaviour, delirium, septic encephalopathy, multiple sclerosis, alzheimer’s disease
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 390185
URI: http://eprints.soton.ac.uk/id/eprint/390185
ISSN: 0889-1591
PURE UUID: 03d4cd78-97d0-413f-a577-4ecbdf83f3ae
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Date deposited: 22 Mar 2016 09:08
Last modified: 15 Mar 2024 04:03
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