The Grasshopper: A Novel Model for Assessing Vertebrate Brain Uptake

@article{Andersson2013TheGA,
  title={The Grasshopper: A Novel Model for Assessing Vertebrate Brain Uptake},
  author={Olga Andersson and Steen Honor{\'e} Hansen and Karin Hellman and Line R{\o}rb{\ae}k Olsen and Gunnar Andersson and Lassina Badolo and Niels Svenstrup and Peter Aadal Nielsen},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2013},
  volume={346},
  pages={211 - 218}
}
The aim of the present study was to develop a blood-brain barrier (BBB) permeability model that is applicable in the drug discovery phase. The BBB ensures proper neural function, but it restricts many drugs from entering the brain, and this complicates the development of new drugs against central nervous system diseases. Many in vitro models have been developed to predict BBB permeability, but the permeability characteristics of the human BBB are notoriously complex and hard to predict… Expand
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An Insect-Based Ex Vivo Blood Brain Barrier Efflux Assay
Drug efflux activity of ABC transporters, at the human blood brain barrier (BBB), constitutes a crucial challenge for central nervous system (CNS) drug development. Accordingly, early screening of… Expand
Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model
TLDR
It is shown that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery and to retain the major cues that maintain and modulate the physiological function of the brain barrier. Expand
Development of an a priori computational approach for brain uptake of compounds in an insect model system.
TLDR
The results indicate that the locust insect model is amenable to data mining chemoinformatics and in silico model development in CNS drug discovery pipelines. Expand
An invertebrate model for CNS drug discovery: Transcriptomic and functional analysis of a mammalian P-glycoprotein ortholog.
TLDR
Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery. Expand
Barrier mechanisms in the Drosophila blood-brain barrier
TLDR
Findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. Expand
Molecular determinants of blood-brain barrier permeation.
TLDR
The different computational tools available today, as well as the experimental methods used to determine BBB permeability, are explored, which include in vitro models and the in vivo models that yield the dataset the authors use to generate predictive models. Expand
Identification of a Functional Homolog of the Mammalian CYP3A4 in Locusts
TLDR
Not only may locusts be a model useful for determining BBB permeation, but possibly insects could be used in metabolism investigation, however, extensive characterization of the insect model is necessary to determine its applicability. Expand
Identification of a Functional Homolog of the Mammalian CYP 3 A 4 in Locusts Line
Insects have been proposed as a new tool in early drug development. It was recently demonstrated that locusts have an efflux transporter localized in the blood-brain barrier (BBB) that is… Expand
An ex Vivo Model for Evaluating Blood-Brain Barrier Permeability, Efflux, and Drug Metabolism.
TLDR
Overall, the experiments indicated that invertebrates might be useful for screening of blood-brain barrier permeation, efflux, metabolism, and analysis of the unbound fraction of drugs in the brain in early drug discovery. Expand
Development of a sensitive and quantitative capillary LC-UV method to study the uptake of pharmaceuticals in zebrafish brain
TLDR
Quantitative experiments carried out on pooled samples of six zebrafish demonstrated the selective semipermeable nature of the blood-brain barrier after incubating the zebra fish at the maximum tolerated concentration for the investigated pharmaceuticals. Expand
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References

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