ABSTRACT

Delivery of neuroprotective or therapeutic agents to specific regions of the brain presents a major challenge, largely due to the presence of the Blood-Brain Barrier (BBB). The BBB is formed by capillary endothelial cells, surrounded by basal lamina and astrocytic perivascular endfeet with astrocytes providing the cellular link to the neurons. In parallel to the efforts focused on drug delivery across the BBB, there has been a recent interest and surge of literature describing the effects of nanoparticles on the BBB. The presence of the tight junctions is responsible for development of the polarized membranes that regulate transport across the BBB using both active and efflux transporters. Astrocytes are also known to secrete a large number of substances including peptides, growth factors and chemokines which modulate the BBB function. Pericytes also secrete factors that modulate BBB such as transforming growth factor-ß and glial cell-derived neurotrophic factor that increase production of tight junction proteins comprising of claudins, occludin and cytoplasmic proteins.