Investigating the Blood Brain Barrier in HIV+ Substance Users
HIV entry into the brain is mediated, at least in part, by infected monocyte transmigration across the blood brain barrier (BBB). These monocytes are productively infected with HIV and primed to cross the BBB. Once within the CNS, they may differentiate into infected macrophages that can persist for years. We, in collaboration with the Berman Lab at Albert Einstein College of Medicine, aim to examine molecular mechanisms of HIV-mediated neuroinflammation in the presence of ART and opiods. We will study the effects of morphine as it exacerbates inflammation and CNS disease in many HIV infected people, and methamphetamine (meth) as it increases brain viral load in HIV replication in human macrophages and microglia, and compromises the blood brain barrier (BBB) and mediates immune activation.
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Functional evaluation of the effect of HIV infection and meth exposure on the BBB integrity
We will use a modification of an approach which we have previously reported to demonstrate that HIV infection increases the capacity of monocytes to cross the BBB disrupted by systemic drug treatment