The proposed work derives from observations of neuronal disease progression in people with the acquired immunodeficiency syndrome (AIDS), and has as its goal the use of MRS for the non-invasive quantification of neuronal loss, neuronal dysfunction, and brain metabolic abnormalities in a simian model of the AIDS dementia complex (ADC). The Investigator postulates that neuropathological events similar to those experienced after HIV infection occur subsequent to infection with SIV in the SIV macaque model. Currently, no simple, reliable, and non-invasive methods are available with which to assess the progressive neurological injury associated with AIDS in vivo; MRS has the capability to provide such assessments. The Investigator proposes to quantify the neuronal injury sustained after SIV infection directly through MRS measurements of N-acetyl aspartate (NAA), a molecule which resides exclusively in neurons, and to monitor any variation in other brain metabolic markers, in particular, choline containing metabolites, by MRS.
The specific aims are: (1) to quantify noninvasively by proton MRS imaging, the regional distribution, pattern and extent of changes in NAA and other metabolites in the SIV-infected macaque in vivo at different stages of infection; (2) to verify the in vivo measurements by high resolution in vitro spectroscopy of brain extracts from the same animal; (3) to determine the cellular pathology that underlie these metabolic alterations by quantitative studies of neuronal content, synaptic and dendritic density, and astrocytosis; and (4) to determine the relationship of viral localization to the metabolic and pathological abnormalities.
Showing the most recent 10 out of 39 publications
