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Computational Systems Models for Neurovascular Development
Citation:
Knudsen, T. Computational Systems Models for Neurovascular Development. 5th International Conference on Developmental Neurotoxicity Testing (DNT5), Konstanz, GERMANY, April 07 - 10, 2024. https://doi.org/10.23645/epacomptox.25602390
Impact/Purpose:
Presentation or Poster presented to 5th International Conference on Developmental Neurotoxicity Testing (DNT5)
Description:
Computational Systems Models for Neurovascular Development Thomas B. Knudsen, Research Triangle Park, NC Morphogenesis of the blood-brain barrier (BBB) is a complex process linked to neovascularization of the embryonic neural tube. This selective transport interface forms between vascular-neural compartments and its dysregulation has been linked to neuroinflammation and neurodevelopmental defects. Although drugs and chemicals are known to interact with the prenatal BBB, less is known about its potential role in neurodevelopmental toxicity. Microglia, best known as resident macrophages of the brain, have gained attention for their role in BBB morphogenesis and pathogenesis [Naphade et al. (2024) Curr Opin Tox]. Microglial cells support microvascular arborization and barriergenesis. Their precursors originate in hematopoietic blood islands of the embryonic yolk sac, emigrate to the anterior neural tube, colonize the neural epithelium ahead of vascularization, and interact with angiogenic sprouts from the perineural vascular plexus. To evaluate microglial dynamics, we built an agent-based model of the neurovascular unit (cNVU). The computer model simulates interactions between neuroprogenitor cells, microglia, and endothelial cells on a cell-by-cell and interaction-by-interaction basis. The computational-in vitro integrated approach enables a unique way to translate disruption of microglial response to chemical exposure and can be used to predict adverse consequences on BBB development at a morphological level. Disclaimer: abstract does not necessarily reflect the views or policies of the USEPA.
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DOI: Computational Systems Models for Neurovascular Development
DNT5_2024_KNUDSEN_FINAL.PDF (PDF, NA pp, 3600.49 KB, about PDF)