MATH MODEL OF EXTRAVASATION OF LEUKOCYTES IN SIV INFECTION IN RHESUS MACAQUES

这个子项目是众多研究子项目之一

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. The trafficking of leukocytes through the blood brain barrier in the presence of disease, as in the case of human AIDS, is too complicated to understand intuitively. We have developed a protocol utilizing the techniques of immunohistochemistry and confocal microscopy to achieve simultaneous detection and visualization of cell populations and signals involved in the neuropathogenesis of AIDS. However, the number of cells and cytokines produced during neuroinvasion are far too numerous to accurately gain an understanding of their activities in response to infection. Therefore, we have begun developing a mathematical model to track the leukocyte extravasation at the BBB in order to accommodate the major activities of the cytokines and to establish a sequence in which these cells arrive to deliver the virus into the brain. Although the pathogenesis is still unclear, we propose that SIV-infected macrophages producing IL-6 are the first cells to arrive, followed by T-cells producing IL-6 and IFN-¿, and finally macrophages producing TNF-¿ or ¿. This study discusses the techniques carried out to develop this model and attempts to qualitatively examine this system of infection to ultimately propose points of interference that could lead to advancements in the treatment of HIV and possible prevention of such infections into the brain.