Physiology and pathology of the blood-brain barrier: implications for microbial pathogenesis, drug delivery and neurodegenerative disorders.

The blood-brain barrier (BBB) regulates the passage of solutes between the CNS and the blood. The BBB not only restricts the entry of serum proteins into the CNS, but it also controls the passage of nutrients, electrolytes, vitamins, minerals, free fatty acids, peptides, and regulatory proteins in both the brain to blood and blood to brain direction. The BBB performs these functions through a number of saturable and non-saturable mechanisms. For example, efflux (CNS to blood) mechanisms regulate the levels of nutrients and minerals in the CSF, detoxify the CNS, reinforce the impermeability of the BBB against circulating toxins and many drugs, secrete CNS-originating substances into the blood, and drain substances directly into the cervical lymphatic nodes. Influx mechanisms control the homeostatic environment of the CNS, supply the brain with nutrients, and help to integrate CNS and peripheral functions. These mechanisms are altered in and can be the basis for disease and many of these systems are altered in neuroAIDS. We review here examples of several diseases in which the functions of the BBB are altered, and some conditions, such as alcoholism, multiple sclerosis, obesity, and a subtype of mental retardation, where those altered functions may underlie the pathophysiology. Finally, we consider some of the ways in which these aspects of the BBB could be active in neuroAIDS, including the efflux of anti-virals, the transport of virus by adsorptive endocytosis, egress routes for HIV-1 via brain lymphatics, and the release of neurotoxins from brain endothelial cells.