BBB Transport Systems in HIV-1 Infection

Yuri Persidsky, MD, Ph.D.; Tsuneya Ikezu, MD Co-Investigator; - University of Nebraska Medical Center, Center for Neurovirology and Neurodegenerative Disorders.

The study will explore how the blood-brain barrier (BBB) is compromised in HIV-1 associated dementia (HAD). A laboratory model of the BBB, severe combined immunodeficiency (SCID) mice with HIV-1 encephalitis (HIVE) and brain autopsy tissue will be employed. Cross-validating results obtained in three diverse biological systems will provide evidence for how the BBB is compromised during HIV-1 disease. We will plan 1) to study expression of specialized transport systems (P-gp, multi-drug resistant proteins and other transporters) on BBB during HAD utilizing autopsy brain tissues; 2) to assess the alterations in specialized transport systems (P-gp and others) during monocyte migration across artificial three-dimensional BBB model or SCID mouse model for HIVE; 3) to correlate structural-functional alterations of BBB detected by neuroimaging techniques with motor/cognitive abnormalities in SCID mouse model for HIVE.