Evidence map›Paper›PMID 31703066›Full record

ArticlePloS one2019

Three-dimensional (3D) brain microphysiological system for organophosphates and neurochemical agent toxicity screening.

Lumei Liu, Youngmi Koo, Chukwuma Akwitti, Teal Russell, Elaine Gay, Daniel T Laskowitz, Yeoheung Yun

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  7. Towards Novel BiomimeticBioengineering (Basel, Switzerland) · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Microphysiological systems: What it takes for community adoption.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  13. Review
  14. Review
  15. Review
  16. Emerging Neuroblastoma 3DFrontiers in immunology · 2020
    Review
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Lumei LiuFIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
Youngmi KooFIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
Chukwuma AkwittiFIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
Teal RussellFIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
Elaine GayCenter for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina, United States of America.
Daniel T LaskowitzDepartments of Neurology, Anesthesiology, and Neurobiology, Brain Injury Translational Research Center, Duke University, Durham, North Carolina, United States of America.
Yeoheung YunFIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.ORCID 0000-0003-2288-6052
North Carolina Agricultural and Technical State University · USDuke University · USRTI International · US

Funding

Studying Interface Behavior of Blood and Degradable Magnesium StentSC3GM113728 · NIGMS · NORTH CAROLINA AGRI & TECH ST UNIV · PI YUN, YEOHEUNG · 2015 to 2018
$432k
NIGMS NIH HHS SC3 GM113728
6 · The paper itself

Abstract

We investigated a potential use of a 3D tetraculture brain microphysiological system (BMPS) for neurotoxic chemical agent screening. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded neuroblastoma cells, microglia, and astrocytes, and vascular tissue with dynamic flow and membrane-free culture of the endothelial layer. We tested the broader applicability of this model, focusing on organophosphates (OPs) Malathion (MT), Parathion (PT), and Chlorpyrifos (CPF), and chemicals that interact with GABA and/or opioid receptor systems, including Muscimol (MUS), Dextromethorphan (DXM), and Ethanol (EtOH). We validated the BMPS platform by measuring the neurotoxic effects on barrier integrity, acetylcholinesterase (AChE) inhibition, viability, and residual OP concentration. The results show that OPs penetrated the model blood brain barrier (BBB) and inhibited AChE activity. DXM, MUS, and EtOH also penetrated the BBB and induced moderate toxicity. The results correlate well with available in vivo data. In addition, simulation results from an in silico physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model that we generated show good agreement with in vivo and in vitro data. In conclusion, this paper demonstrates the potential utility of a membrane-free tetraculture BMPS that can recapitulate brain complexity as a cost-effective alternative to animal models.

Indexed as

Imaging, Three-DimensionalToxicity TestsAcetylcholinesteraseAnimalsBrainCell LineCell SurvivalMiceMicrofluidicsNeurotoxinsOrganophosphatesReceptors, GABAReceptors, OpioidTime FactorsAcetylcholinesteraseNeurotoxinsOrganophosphatesReceptors, GABAReceptors, Opioid

Identifiers

PMID31703066
PMCPMC6839879
OpenAlexW2983358385

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.