EPA Science Inventory

Computational modeling of the neurovascular unit to predict microglia mediated effects on blood-brain barrier formation (WC10)

Citation:

Zurlinden, T., K. Saili, A. Silvin, A. Schwab, S. Hunter, N. Baker, F. Ginhoux, AND T. Knudsen. Computational modeling of the neurovascular unit to predict microglia mediated effects on blood-brain barrier formation (WC10). Presented at Tenth World Congress, Seattle, Washington, August 20 - 24, 2017.

Description:

Development of the neurovascular unit (NVU) involves interactions between endothelial cells, pericytes, neuroprogenitor cells, and microglia. We constructed an in silico model of the developing neuroepithelium in CompuCell3D which recapitulated a suite of critical signaling pathways (Notch/dll4, CSF-1, VEGF-A/C) and cellular behaviors (growth, migration, proliferation, differentiation, apoptosis). Imputing ToxCast in vitro profiling data into the simulated neuroepithelium enabled predictions of developmental neurovascular toxicity. For example, targeting CSF-1R in silico yielded a quantitative effect on microvascular arborization. Cybermorphs can now be qualified against in vivo phenotypes from CSF-1R ablation genetically or immunologically. The in silico models, combined with in vitro cell-level data, can guide engineering of human cell-based NVU-devices to prioritize untested environmental chemicals for further testing. This abstract does not reflect US EPA policy.

Purpose/Objective:

Presentation at the 10th World Congress. Implementation of an in silico model of the developing neuroepithelium in CompuCell3D to recapitulate a suite of critical signaling pathways (Notch/dll4, CSF-1, VEGF-A/C) and cellular behaviors (growth, migration, proliferation, differentiation, apoptosis).

URLs/Downloads:

WC10_CNVU_JOINT ABSTRACT_FINAL.PDF   (PDF,NA pp, 18.176 KB,  about PDF)

CNVU_ZURLINDEN_20170815_FINAL_M.PDF   (PDF,NA pp, 2887.058 KB,  about PDF)

Record Details:

Record Type: DOCUMENT (PRESENTATION/SLIDE)
Start Date: 08/24/2017
Completion Date: 08/24/2017
Record Last Revised: 03/20/2018
Record Created: 03/13/2018
Record Released: 03/13/2018
OMB Category: Other
Record ID: 340063

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL CENTER FOR COMPUTATIONAL TOXICOLOGY