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Blood-Brain-Barrier Morphogenesis: A Case Example of Rapid Review Approaches Informing Predictive Toxicity Models
Citation:
Knudsen, T. Blood-Brain-Barrier Morphogenesis: A Case Example of Rapid Review Approaches Informing Predictive Toxicity Models. Society for Birth Defects Research and Prevention 63rd Annual Conference, Charleston, SC, June 24 - 28, 2023. https://doi.org/10.23645/epacomptox.24250357
Impact/Purpose:
This is an invited presentation in a symposium entitled 'Characterizing Developmental and Reproductive Hazards Using Rapid Review Tools' to be presented at the annual conference of the Society for Birth Defects Research and Prevention (BDRP) in June 2023.
Description:
Morphogenesis of the blood-brain barrier (BBB) is a complex process linked to neovascularization of the neural tube. The process involves regulation of angiogenic sprouting and microvascular differentiation to create a selective transport interface between vascular-neural compartments during organogenesis. Several cell types contribute to BBB morphogenesis, including endothelial cells, pericytes, neural stem cells, and microglia. The latter derive from hematopoietic blood islands of the yolk sac and colonize the neural epithelium ahead of vascular ingression. Microglia play a key role in neuro-vascular coupling. Despite an extensive literature base, many gaps remain in our understanding for how this resident immunological sentinel interacts with chemical exposure during neurodevelopment. Here, we used AbstractSifter as a rapid review tool to build and filter a corpus of 19,850 publications focused on relevant molecular functions, signaling events, cellular behaviors, and biological processes scoping microglial dynamics and toxicity. Whereas a large body of that work focused on neurodevelopment, neuroinflammation, and neurodegeneration, here we focus on a subset of the corpus supporting first principles in the events underlying neovascularization of the neural tube and brain embryology. Goals were to: (i) synopsize current understanding of microglial function during BBB morphogenesis; (ii) evaluate potential disruption of microglial function linked to molecular initiating events (MIEs) invoked by drug/chemical exposure during pregnancy; and (iii) integrate this information into a working prototype computational (in silico) model for predictive toxicity of developmental BBB dysfunction. This abstract does not represent the views of the Agency.
URLs/Downloads:
DOI: Blood-Brain-Barrier Morphogenesis: A Case Example of Rapid Review Approaches Informing Predictive Toxicity Models
BDRP_2023_KNUDSEN_06132023_V2.PDF (PDF, NA pp, 5873.455 KB, about PDF)