Impact of Inflammation on the Blood-Neural Barrier and Blood-Nerve Interface: From Review to Therapeutic Preview.

Abstract

A number of nervous system disorders are characterized by a state of inflammation (neuroinflammation) in which members of the innate immune system, most notably mast cells and microglia-acting as single entities and in unison-produce inflammatory molecules that play major roles. A neuroinflammatory environment can weaken not only blood-nerve and blood-brain barrier (BBB) integrity but also that of the blood-spinal cord barrier. Mast cells, with their distribution in peripheral nerves and the central nervous system, are positioned to influence blood-nerve barrier characteristics. Being close also to the perivasculature and on the brain side of the BBB, the mast cell is well positioned to disrupt BBB function. Interestingly, tissue damage and/or stress activates homeostatic mechanisms/molecules expressed by mast cells and microglia, and includes N-acylethanolamines. Among the latter, N-palmitoylethanolamine has distinguished itself as a key component in supporting homeostasis of the organism against external stressors capable of provoking inflammation. This review will discuss the pathobiology of neuroinflammation with emphasis on mast cells and microglia, their roles in BBB health, and novel therapeutic opportunities, including nanoscale delivery for targeting these immune cells with a view to maintain the BBB.