A Review of Blood-Brain Barrier Transport Techniques

The blood-brain barrier (BBB) is a unique dynamic regulatory interface situated at the border between the blood stream and the brain extracellular (or interstitial) fluid. As the “gatekeeper” to the brain, it determines the ability of drugs to gain entrance to brain extracellular fluid and reach therapeutic concentrations within the central nervous system (CNS) (1 ,2 ). The BBB also protects the brain from circulating neuroactive solutes, such as glutamate, glycine, norepinephrine, epinephrine, and peptide hormones, which can increase with diet, stress, injury, or disease (3 ). The BBB has an insulating function restricting brain access of many natural toxins, metals, antibodies, and biologic complexes and, in many cases, actively removing such from brain by energy-dependent efflux (4 ). The BBB has a key regulatory role in facilitating brain uptake of essential nutrients, vitamins, and hormones to sustain cerebral growth and metabolism, and in maintaining cerebral ionic and volume balance (3 ,5 ,6 ). In the absence of a BBB, the CNS would be constantly rocked by simple alterations during the acts of daily living, such as increased levels of neurotransmitters in the “fight-or-flight” response or exposure to plant toxins (e.g., ivermectin) from novel food stuffs, that would impede higher mental function. Our view of the BBB has evolved dramatically over the past 20 years from a simple restrictive interface that impedes the diffusion of polar solutes into brain, into a dynamic, highly selective, regulatory interface that expresses a wide range of active and facilitated transport systems and that responds to alterations in environment to maintain optimal cerebral homeostasis.