PMID- 32590145
OWN - NLM
STAT- MEDLINE
DCOM- 20220307
LR  - 20221223
IS  - 1873-1708 (Electronic)
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 96
DP  - 2020 Sep
TI  - A cross-platform approach to characterize and screen potential neurovascular unit 
      toxicants.
PG  - 300-315
LID - S0890-6238(20)30169-6 [pii]
LID - 10.1016/j.reprotox.2020.06.010 [doi]
AB  - Development of the neurovascular unit (NVU) is a complex, multistage process that 
      requires orchestrated cell signaling mechanisms across several cell types and 
      ultimately results in formation of the blood-brain barrier. Typical 
      high-throughput screening (HTS) assays investigate single biochemical or single 
      cell responses following chemical insult. As the NVU comprises multiple cell 
      types interacting at various stages of development, a methodology combining 
      high-throughput results across pertinent cell-based assays is needed to 
      investigate potential chemical-induced disruption to the development of this 
      complex cell system. To this end, we implemented a novel method for screening 
      putative NVU disruptors across diverse assay platforms to predict chemical 
      perturbation of the developing NVU. HTS assay results measuring chemical-induced 
      perturbations to cellular key events across angiogenic and neurogenic outcomes in 
      vitro were combined to create a cell-based prioritization of NVU hazard. 
      Chemicals were grouped according to similar modes of action to train a logistic 
      regression literature model on a training set of 38 chemicals. This model 
      utilizes the chemical-specific pairwise mutual information score for PubMed MeSH 
      annotations to represent a quantitative measure of previously published results. 
      Taken together, this study presents a methodology to investigate NVU 
      developmental hazard using cell-based HTS assays and literature evidence to 
      prioritize screening of putative NVU disruptors towards a knowledge-driven 
      characterization of neurovascular developmental toxicity. The results from these 
      screening efforts demonstrate that chemicals representing a range of putative 
      vascular disrupting compound (pVDC) scores can also produce effects on neurogenic 
      outcomes and characterizes possible modes of action for disrupting the developing 
      NVU.
CI  - Published by Elsevier Inc.
FAU - Zurlinden, Todd J
AU  - Zurlinden TJ
AD  - U.S. Environmental Protection Agency, Office of Research and Development, Center 
      for Computational Toxicology and Exposure, United States.
FAU - Saili, Katerine S
AU  - Saili KS
AD  - U.S. Environmental Protection Agency, Office of Research and Development, Center 
      for Computational Toxicology and Exposure, United States.
FAU - Baker, Nancy C
AU  - Baker NC
AD  - Leidos, United States.
FAU - Toimela, Tarja
AU  - Toimela T
AD  - FICAM, Faculty of Medicine and Health Technology, Tampere University, Finland.
FAU - Heinonen, Tuula
AU  - Heinonen T
AD  - FICAM, Faculty of Medicine and Health Technology, Tampere University, Finland.
FAU - Knudsen, Thomas B
AU  - Knudsen TB
AD  - U.S. Environmental Protection Agency, Office of Research and Development, Center 
      for Computational Toxicology and Exposure, United States. Electronic address: 
      knudsen.thomas@epa.gov.
LA  - eng
GR  - EPA999999/ImEPA/Intramural EPA/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200624
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Hazardous Substances)
SB  - IM
MH  - Biological Assay
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/physiology
MH  - Fibroblasts/drug effects
MH  - Hazardous Substances/*toxicity
MH  - *High-Throughput Screening Assays
MH  - Humans
MH  - Neovascularization, Physiologic/drug effects
MH  - Nerve Net/drug effects
MH  - Neural Crest/drug effects
MH  - Neural Stem Cells/drug effects
MH  - Neurogenesis/drug effects
PMC - PMC9773816
MID - NIHMS1679654
OTO - NOTNLM
OT  - Angiogenesis
OT  - Neurogenesis
OT  - Predictive toxicology
OT  - ToxCast
EDAT- 2020/06/27 06:00
MHDA- 2022/03/08 06:00
PMCR- 2022/12/22
CRDT- 2020/06/27 06:00
PHST- 2019/12/10 00:00 [received]
PHST- 2020/05/28 00:00 [revised]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2022/03/08 06:00 [medline]
PHST- 2020/06/27 06:00 [entrez]
PHST- 2022/12/22 00:00 [pmc-release]
AID - S0890-6238(20)30169-6 [pii]
AID - 10.1016/j.reprotox.2020.06.010 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2020 Sep;96:300-315. doi: 10.1016/j.reprotox.2020.06.010. Epub 
      2020 Jun 24.