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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。研究表明许多不同类型的细胞参与了艾滋病的神经发病。这包括居住在中枢神经系统（CNS）的细胞，如血管周围巨噬细胞、实质小胶质细胞、星形胶质细胞、内皮细胞和神经元，以及从周围进入大脑的细胞，如T细胞和单核细胞。大多数证据表明，血管周围巨噬细胞是产生性HIV/SIV感染的主要目标，涉及的细胞类型和细胞信号分子（细胞因子、趋化因子、粘附分子）的数量太多，无法准确地直观地了解它们对感染的反应活性。出于这个原因，必须采取另一种方法来允许对系统进行更详细的调查，以便量化所产生的事件。数学模型在许多科学相关领域被用来分析特定系统的详细组成部分。因此，我们已经开始开发一个专注于神经侵入的数学模型来检查白细胞外渗，包括信号和参与的细胞，以更好地理解这一过程。这个系统的建模将允许调节细胞因子的主要活动，以及建立一个序列，在这个序列中，参与神经入侵的细胞从血脑屏障（BBB）外渗，传递病毒或到达大脑对抗感染。该模型基于多标记共聚焦显微镜检查siv感染猕猴中枢神经系统中细胞因子产生细胞和病毒感染细胞的存在位置和免疫表型。

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.