Session 18Oral Abstract Presentations Viral Neuropathogenesis Session Day and Time: Wednesday 10 am - 12:30 pm Presentation Time: 11:45 Room: Ballroom C
93 Tracking Movement of Super-paramagnetic Iron Oxide Labeled Monocytes in Brain by High Field Magnetic Resonance Imaging: Relevance for HIV-1 Associated Dementia M. Zelivyanskaya*1, J. Nelson1, L. Poluektova1, M. Uberti2, M. Boska1, H. Gendelman1 1Univ of Nebraska Med Ctr, Omaha and 2Univ of Nebraska, Omaha
Background: An unresolved question for HIV encephalitis and its associated dementia is how few infected brain mononuclear phagocytes (MP; brain macrophages and microglia) cause wide-spread neuronal damage. One hypothesis is that MP pro-inflammatory secretory products incite an amplification of inflammatory neurotoxic activities from neighboring glial cells. Alternately, monocytes entering the brain become immune competent, are mobile, and affect neural function at a distance.
Methods: To address the latter, human monocytes were labeled with super-paramagnetic iron oxide, Feridex (2 mg/ml/hr), injected stereotactically into basal ganglia of severe combined immunodeficient mice, and cell migration monitored sequentially from 1-14 days by a high-field 7 Tesla magnetic resonance imaging (MRI) system. MRI tests used to track cell movement was verified by histological co-registration for microglia and astrocyte antigens and for cellular activation.
Results: Feridex labeled monocytes were 99% viable and chemotactic in laboratory tests. Human monocyte-derived macrophages migrated through interstitial fluids, across the corpus collosum and white matter tracks. Cells were found concentrated along the site of injection, but also were detected, at lower numbers, throughout the ventricular system with a diffuse distribution that included the contralateral hemisphere up to 14 days.
Conclusions: These data support the idea that monocytes migrate through multiple brain anatomical structures and, by this way, can affect the neuro degeneration commonly seen during HIV-associated dementia.
