The Blood-Brain Barrier and Its Role in Inflammation

Abstract

The unique microenvironment within the central nervous system (CNS) relies upon the integrity of the blood-brain barrier (BBB). This selectively permeable barrier comprises interendothelial tight junctions located at the capillaries and postcapillary venules. Cells and structures in the local environment are required to maintain normal BBB function. When inflammation is present, the BBB itself plays an integral role in the inflammatory response by either producing or expressing a variety of cytokines, adhesion molecules, metalloproteinases, serine proteases, products of arachidonic acid metabolism, and nitric oxide. Understanding the role of the BBB during inflammation is essential when creating and employing a therapeutic regime for animals with CNS disease. This review focusses on recent discoveries about the BBB and its role in inflammation, and applies this knowledge to our current understanding of inflammatory CNS disease in dogs and cats.

Protection after stroke: cellular effectors of neurovascular unit integrity

“…Additionally, BBB disruption coincides with the induction of aquaporin 4 (AQP4) expression and the presence of reactive astrocytes in the perivascular glial cells (Tran et al, 1999; Lo et al, 2003; Tomás-Camardiel et al, 2005; Vakili et al, 2005). Several chemical agents circulating in the plasma or secreted from cells associated with the BBB are capable of increasing brain endothelial permeability and impairing its transport and metabolic functions (Laflamme et al, 1999; Abbott, 2000; Webb and Muir, 2000). These agents include histamine, serotonin, glutamate, purine nucleotides (ATP, ADP, and AMP), adenosine, platelet-activating factor, phospholipase A2, arachidonic acid, prostaglandins, leukotrienes, tumor necrosis factor-α (TNFα), free radicals and nitric oxide (Laflamme et al, 1999; Abbott, 2000; Webb and Muir, 2000; Tan et al, 2002; Stolp and Dziegielewska, 2009).…”

Inflammation induced at different developmental stages affects differently the range of microglial reactivity and the course of seizures evoked in the adult rat

“…During the inflammatory status, endothelial and blood-derived cells, microglia, and astrocytes are involved in enhanced cytokine production resulting, in turn, in activation of metalloproteinases and catabolism of arachidonic acid [2][3][4]. Proinflammatory factors such as IL-1β or TNFα can directly increase neuronal excitability and facilitate spontaneous seizure activity [5].…”

On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update

“…Inflammation in the brain and immune activation are processes widely involved in the pathophysiology of neurodegenerative diseases; during these events, the BBB becomes more permeable, then contributing to disease progression and severity (Webb and Muir, 2000).…”