PMC:7463108 / 60777-62474 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7463108","sourcedb":"PMC","sourceid":"7463108","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7463108","text":"Taken together, BBB damage from HIV and/or opiates can disrupt the homeostasis within the brain. Breakdown of paracellular processes, through decreases in tight junction proteins and increased cellular adhesion proteins, increased leakage of circulating molecules into the brain and increased monocyte/MDM adhesion and transmigration into the brain, which if infected, can serve to replenish viral reservoirs within the CNS. Furthermore, alterations in drug transport proteins within the brain can decrease ARV efficacy by decreasing drug concentrations. Collectively, these changes serve to maintain HIV infection within the brain (see Fig. 4; Tables 1 and 2).\nFig. 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 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