Brain barriers and the acute-phase response

Abstract

[Excerpt] Recent findings on the brain response to peripheral inflammation have broadened our knowledge on the acute phase response. Notably, such advances may lead to the characterization of acute phase proteins in body fluids other than the blood. Among these, and of particular interest, is the cerebrospinal fluid (CSF) that fills the brain ventricles, the subarachnoid space and the spinal cord. Acute phase response is a term used to describe, mostly, the liver response to an inflammatory insult, a process that, among other effects, ultimately results in changes in the plasma concentrations of various proteins. The triggers of liver response include the inflammatory insult and the molecules produced by multiple cell types, from inflammatory cells (e.g. neutrophils and macrophages), to endothelial and liver cells. As a consequence, the liver synthesizes a number of so-termed acute phase proteins that are classified, depending on whether their expression is increased or decreased, as positive or negative acute phase response proteins, respectively. Among the positive acute phase proteins are binding proteins, opsonins (e.g. C-reactive protein) and iron-related proteins [e.g. hepcidin (HAMP), ceruloplasmin, lipocalin 2 (LCN2) and ferritin]. The negative acute phase proteins also include binding proteins (e.g. albumin, transthyretin, retinol-binding protein), as well as iron-related proteins (e.g. transferrin). Nonetheless, acute phase response is not a process restricted to the liver. Throughout the years, acute phase proteins expression has also been found altered at the barriers of the brain. Most of these findings originated from work on the brain parenchyma response to inflammation (Quan et al., 1998; Nadeau & Rivest, 1999); however, surprisingly, only recently were the barriers of the brain specifically considered in the overall response to peripheral inflammation. In this chapter we will address the contribution of the barriers of the brain in the acute-phase response to peripheral inflammatory stimuli. [...]