ArticleFluids and barriers of the CNS2016
In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs).
Article in Fluids and barriers of the CNS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
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- The Bradykinin B2 Receptor Agonist (NG291) Causes Rapid Onset of Transient Blood-Brain Barrier Disruption Without Evidence of Early Brain Injury.Frontiers in neuroscience · 2021Article
- A peptide for transcellular cargo delivery: Structure-function relationship and mechanism of action.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review.RSC advances · 2020Review
- Tissue-engineered blood-brain barrier models via directed differentiation of human induced pluripotent stem cells.Scientific reports · 2019Article
- An experimentally validated approach to calculate the blood-brain barrier permeability of small molecules.Scientific reports · 2019Article
- Benchmarking in vitro tissue-engineered blood-brain barrier models.Fluids and barriers of the CNS · 2018Review
- Ebola Virus Delta Peptide Is a Viroporin.Journal of virology · 2017Article
- Engineering the human blood-brain barrier in vitro.Journal of biological engineering · 2017Review
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4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection.
methodsTo assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion.
resultsThe permeability of 2-PAM is about 2 × 10(-6) cm s(-1) in MDCK cells and about 1 × 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps.
conclusionsThe low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning.
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