PMID- 29251840
OWN - NLM
STAT- MEDLINE
DCOM- 20180810
LR  - 20200225
IS  - 2472-1727 (Electronic)
VI  - 109
IP  - 20
DP  - 2017 Dec 1
TI  - Blood-brain barrier development: Systems modeling and predictive toxicology.
PG  - 1680-1710
LID - 10.1002/bdr2.1180 [doi]
AB  - 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.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Saili, Katerine S
AU  - Saili KS
AUID- ORCID: 0000-0001-5759-1006
AD  - National Center for Computational Toxicology (NCCT); U.S. Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711.
FAU - Zurlinden, Todd J
AU  - Zurlinden TJ
AUID- ORCID: 0000-0003-1372-3913
AD  - National Center for Computational Toxicology (NCCT); U.S. Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711.
FAU - Schwab, Andrew J
AU  - Schwab AJ
AUID- ORCID: 0000-0002-1517-4308
AD  - National Health and Environmental Effects Research Laboratory (NHEERL), U.S. 
      Environmental Protection Agency, Office of Research and Development, Research 
      Triangle Park, North Carolina 27711.
FAU - Silvin, Aymeric
AU  - Silvin A
AD  - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research 
      (A*STAR), 138648, Singapore.
FAU - Baker, Nancy C
AU  - Baker NC
AUID- ORCID: 0000-0002-8351-9435
AD  - Leidos, contractor to NCCT, Research Triangle Park, North Carolina 27711.
FAU - Hunter, E Sidney 3rd
AU  - Hunter ES 3rd
AD  - National Health and Environmental Effects Research Laboratory (NHEERL), U.S. 
      Environmental Protection Agency, Office of Research and Development, Research 
      Triangle Park, North Carolina 27711.
FAU - Ginhoux, Florent
AU  - Ginhoux F
AUID- ORCID: 0000-0002-2857-7755
AD  - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research 
      (A*STAR), 138648, Singapore.
FAU - Knudsen, Thomas B
AU  - Knudsen TB
AUID- ORCID: 0000-0002-5036-596X
AD  - National Center for Computational Toxicology (NCCT); U.S. Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711.
LA  - eng
GR  - EPA999999/Intramural EPA/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/*pathology
MH  - Brain/*blood supply/drug effects/*pathology
MH  - Humans
MH  - *Systems Biology
MH  - *Toxicology
PMC - PMC6476421
MID - NIHMS1510074
OTO - NOTNLM
OT  - blood-brain barrier
OT  - brain
OT  - children's environmental health
OT  - embryo
OT  - neurovascular development
OT  - neurovascular unit
OT  - predictive toxicology
COIS- 6. Conflict of interest statement The authors declare no conflicts.
EDAT- 2017/12/19 06:00
MHDA- 2018/08/11 06:00
PMCR- 2019/04/22
CRDT- 2017/12/19 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2017/11/12 00:00 [accepted]
PHST- 2017/12/19 06:00 [entrez]
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2018/08/11 06:00 [medline]
PHST- 2019/04/22 00:00 [pmc-release]
AID - 10.1002/bdr2.1180 [doi]
PST - ppublish
SO  - Birth Defects Res. 2017 Dec 1;109(20):1680-1710. doi: 10.1002/bdr2.1180.