MR SPECTROSCOPY IN THE SIV INFECTED MACAQUE MODEL OF NEUROAIDS

Harvard Medical School, Boston MA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal is to elucidate the pathways that lead to cerebral injury by HIV infection. Without effective antiretroviral therapy (ART) treatment, approximately one third of AIDS patients will suffer from NeuroAIDS. A leading theory for the pathogenesis of neuroAIDS is that a specific bone marrow derived blood monocyte is virally infected and activated, then traffics into the CNS where it becomes a perivascular macrophage, setting off a cascade of events that result in neuronal injury. We seek to understand the dynamics of monocytic phagocyte (MP) trafficking, MP turnover in the CNS and neuronal recovery. Moreover, the persistence of cumulative neurological disease despite highly active antiretroviral therapy (HAART) has led to a search for adjunctive therapies. Recently, minocycline, a well-tolerated, inexpensive antibiotic has been tested on a variety of neuronal diseases, including NeuroAIDS. However, minocycline's mechanism of action towards HIV-associated neurocognitive disorders (HAND) remains unclear. The goal of our study is to unravel minocycline's mechanism(s) of action. Both goals will be accomplished by evaluating data collected from immunological, immunohistochemical, pathological, and magnetic resonance spectroscopic measurements of SIV-infected rhesus macaque monkeys. To this end we are utilizing the SIV-infected, CD8+ T lymphocyte-depleted macaque model (SIV+/CD8-) which typically results in a reliable accelerated model of neuroAIDS, as 95 percent of persistently (long-term) depleted animals demonstrate histopathological signs of SIV encephalitis.