Transport and Detoxication: Principles, Approaches, and Perspectives for Research on the Blood-Brain Barrier

The blood–brain barrier is an anatomical constraint that maintains homeostasis within the brain and consists of uniquely structured brain capillaries. In addition to these morphological features, a number of specific proteins and transport systems (which are relevant to pharmaceutical applications) can be described that complement barrier functions and ensure a selective supply of substances from the blood to the brain. The additional role of the blood–brain barrier as a site of active detoxication by metabolizing and thus defending against neurotoxic substances has only become apparent in the past few years. Fundamental to understanding these processes are the principles of detoxication reactions and metabolic pathways of excretory organs, which will be described briefly here. The confirmation of these mechanisms in the brain enhances understanding of the complex protective functions of the blood–brain barrier. Evidently, these detoxication pathways simultaneously produce metabolites with neurotoxic or, in case of leukotriene, blood–brain barrier damaging potential. Finally, a detailed description of the mercapturic acid pathway of detoxication will be used to illustrate how evidence of representative enzymes can be used to distinguish definite functions of particular cell types and marker proteins of the blood–brain barrier.