N-acetylcysteine modulation of mitochondrial respiration and blood brain barrier permeability is time dependent and cell type specific

Abstract

The blood brain barrier (BBB) is an active boundary between circulating blood and brain interstitial fluids which functions to regulate the brain’s microenvironment. The barrier restricts transport of cells or toxins into the CNS and regulates the transport of nutrients and metabolites in and out of the brain. The BBB is formed from endothelial cells, adjacent astrocytic end feet, and pericytes of brain vasculature. These cells are connected through a complex set of proteins called tight junctions (TJs) which form a physical barrier forcing most molecules to traffic through tightly controlled, selective transcellular routes–forming a transport barrier. The TJs between endothelial cells are structural proteins responsible for BBB function.1,2 TJs are composed of a combination of trans-membrane and cytoplasmic proteins linked to an action-based cytoskeleton, which allows these junctions to form a tight seal.3 Occludin and the claudins are endothelial TJ proteins that are essential for brain barrier functions.4,5 It has been shown that claudin-5 is a critical regulator of brain endothelial cell permeability.6 Although some evidence indicates that occludin is not essential in the formation of a TJ, its decreased expression has been associated with BBB dysfunction in a number of diseases.7-10