Fig. 4.

Schematic representation of the blood-brain barrier and other components of the neurovascular unit. Under normal conditions (represented above the dotted line), tight junctions are intact which restricts the leakage of paracellular, typically small hydrophilic, compounds, across the barrier and into the brain. Additionally, there is a basal expression of efflux transporters, such as P-glycoprotein (P-gp), which effluxes substrates out of the brain, serving to restrict overall accumulation within the brain. In the setting of HIV and opiate exposure (represented below the dotted line), there is a breakdown of the tight junction proteins and increased leakage of paracellular compounds into the brain. Additionally, opiate exposure increases efflux transporter expression, including P-gp and potentially breast cancer resistance protein (Bcrp), thereby restricting overall brain penetration of drugs (like many antiretroviral drugs) which are substrates for these transporters and in response to HIV and/or opioid exposure.