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. Studies have implicated many different cell types in the neuropathogesis of AIDS. This includes cells resident to the central nervous system (CNS) such as perivascular macrophages, parenchymal microglia, astrocytes, endothelial cells, and neurons as well as cells entering the brain from the periphery such as T cells and monocytes.. . Most evidence indicates that perivascular macrophages are the primary target of productive HIV/SIV infectdion The number of cell types and cell signaling molecules (cytokines, chemokines, adhesion molecules) involved is far too great to accurately gain an intuitive understanding of their activities in response to infection. For this reason, another approach must be taken to allow for a more detailed investigation of the system in order to quantify the resulting events. Mathematical models have been utilized in many science related fields to analyze the detailed components of a particular system. Therefore, we have begun developing a mathematical model focused on neuroinvasion to examine leukocyte extravasation, including signals and cells participating, to better understand this process. Modeling this system will allow for the accommodation of the major activities of the cytokines as well as the establishment of a sequence in which the cells involved in neuroinvasion extravasate from the blood brain barrier (BBB) to deliver the virus or arrive to fight the infection in the brain. The model is based on multilabel confocal microscopy examination of the presence location and immunophenotype of cytokine producing cells and virus infected cells in the CNS of SIV-infected macaques.
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