title: The blood-brain barrier in systemic inflammation.
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 these changes 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.
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Mailpoint 806, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. Electronic address: a.varatharaj@soton.ac.uk.
authors.forename: Aravinthan
authors.initials: A
authors.lastname: Varatharaj
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Mailpoint 806, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. Electronic address: i.galea@soton.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Galea
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology*; D006801:Humans; D007239:Infections / Q000473:pathology*; D007249:Inflammation / Q000503:physiopathology*; D009103:Multiple Sclerosis / Q000503:physiopathology
keywords: Alzheimer’s disease; Blood-brain barrier; Delirium; Lipopolysaccharide; Multiple sclerosis; Septic encephalopathy; Sickness behaviour; Systemic inflammation