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Modeling the role of microglia during neurovascular development (WC10)
Citation:
Saili, K., A. Silvin, T. Zurlinden, A. Schwab, S. Hunter, N. Baker, F. Ginhoux, AND T. Knudsen. Modeling the role of microglia during neurovascular development (WC10). Presented at 10th World Congress: Alternatives and animal use in the life sciences, Seattle, WA, August 20 - 24, 2017.
Impact/Purpose:
Presentation at the 10th World Congress: Alternatives and animal use in the life sciences. We reconstructed complex blood-brain barrier developmental dynamics utilizing computational and molecular methods. These complementary models provide powerful tools for testing the potential roles of microglia in developmental NVU toxicity
Description:
Microglia, resident brain macrophages, have important roles in blood-brain barrier (BBB) development and during focal BBB disruption. We reconstructed these complex dynamics utilizing computational and molecular methods: 1) constructing a systems map of BBB development from known signaling events among cells of the neurovascular unit (NVU), including assay target genes from the ToxCast database; 2) building an agent-based model to recapitulate the reciprocity of microglial (CSF1) x endothelial (VEGF) signals and predict the quantitative impairment of microvascularization during CSF1R inhibition; and 3) testing this prediction utilizing a mouse model wherein embryonic microglia were ablated by anti-CSF1R antibody, and an organotypic culture model of the human NVU on a chip. These complementary models provide powerful tools for testing the potential roles of microglia in developmental NVU toxicity. This abstract does not reflect US EPA policy.