Blood-Brain Barrier During Neuroinflammation

The blood-brain barrier (BBB) shields the brain from the free entry of many toxins and immune cells, thereby providing a specialized environment for neurons and glial cells. In addition, the BBB plays an important role in the regulation and delivery of nutrients to the central nervous system (CNS). During inflammation, many aspects of BBB function are altered. For example, the overproduction of pro-inflammatory molecules by inflammatory and endothelial cells alters BBB transporter functions and thereby increases BBB permeability to neurotoxins and other substances. Inflammation also disrupts junction complexes between brain microvascular endothelial cells, and alters mediators of leukocyte adhesision to endothelial cells, thereby facilitating entry of leukocytes into the brain parenchyma. This chapter explores BBB function in the setting neuroinflammation. The chapter is organized around the following broad areas, all with a focus on the impact of inflammation: signaling mechanisms regulating BBB permeability, endothelial efflux transporters, BBB impairment in neuropathologic conditions, and therapeutic approaches to limiting neruoinflammation. The discussion of therapeutic approaches includes agents that target GSK3 , peroxisome proliferator-activated receptors, progesterone, and statins.