MR SPECTROSCOPY IN THE SIV INFECTED MACAQUE MODEL OF NEUROAIDS

Harvard Medical School, Boston MA

Investigators

Linked publications & trials

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. Neuroinvasion occurs soon after infection and up to 30 percent of those infected with HIV develop AIDS dementia complex (ADC). 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 and sets 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 through an experimental design that tests a series of specific hypotheses derived from the central theory. This will be accomplished by combining immunological, immunohistochemical, pathological, and magnetic resonance spectroscopic measurements of SIV-infected rhesus macaque monkeys. Towards 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;95 percent of persistently (long-term) depleted animals demonstrate histopathological signs of SIV encephalitis.