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A Human Blood-Brain Interface Model to Study Barrier Crossings by Pathogens or Medicines and Their Interactions with the Brain
Published on: April 9, 2019
Blood-brain interfaces and cerebral drug bioavailability.
J-F Ghersi-Egea1, K S Mönkkönen, C Schmitt
1Inserm, U842, faculté de médecine Laennec, université de Lyon, université Lyon-1, UMR-S842, 69008 Lyon, France. jean-francois.ghersi-egea@inserm.fr
Revue Neurologique
|November 17, 2009
Summary
Drug delivery to the brain is challenging due to the blood-brain barrier and blood-cerebrospinal fluid barrier. Understanding efflux transporters is crucial for improving neurological disease treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- The low bioavailability of drugs in the brain hinders the treatment of neurological disorders.
- The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier tightly regulate substance entry into the brain.
- Mechanisms include endothelial tight junctions and efflux transporters, impacting drug distribution.
Purpose of the Study:
- To review the mechanisms limiting drug penetration across blood-brain interfaces.
- To highlight the role of efflux transporters in cerebral drug disposition.
- To discuss implications for neurological disease and brain tumor treatment.
Main Methods:
- Literature review of studies on drug transport across blood-brain interfaces.
- Analysis of the role of tight junctions and efflux transporters (ABC and SLC families).
- Examination of transporter regulation in pathophysiological conditions and development.
Main Results:
- Tight junctions impede water-soluble drugs, while efflux transporters restrict lipid-soluble drugs.
- Efflux transporters significantly impact drug efficacy, especially in brain tumors.
- Transporter expression is altered in conditions like epilepsy and inflammation.
Conclusions:
- Cerebral drug bioavailability is governed by complex interactions at blood-brain interfaces.
- Targeting efflux transporters holds promise for enhancing neurological therapies.
- Further research is needed on transporter development and regulation for optimized drug delivery.
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