Blood-brain barrier development: Systems modeling and predictive toxicology.
Birth Defects Res
; 109(20): 1680-1710, 2017 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-29251840
ABSTRACT
The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites, and hormones between vascular and neural compartments in the brain. Here, we review BBB development with regard to the microphysiology of the neurovascular unit (NVU) and the impact of BBB disruption on brain development. Our focus is on modeling these complex systems. Extant in silico models are available as tools to predict the probability of drug/chemical passage across the BBB; in vitro platforms for high-throughput screening and high-content imaging provide novel data streams for profiling chemical-biological interactions; and engineered human cell-based microphysiological systems provide empirical models with which to investigate the dynamics of NVU function. Computational models are needed that bring together kinetic and dynamic aspects of NVU function across gestation and under various physiological and toxicological scenarios. This integration will inform adverse outcome pathways to reduce uncertainty in translating in vitro data and in silico models for use in risk assessments that aim to protect neurodevelopmental health.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toxicology
/
Brain
/
Blood-Brain Barrier
/
Systems Biology
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Birth Defects Res
Year:
2017
Type:
Article