Chapter 6.4 Microdialysis as a method to study blood-brain barrier transport mechanisms

Abstract

Abstract Often, blood-brain barrier (BBB) transport is still considered qualitatively, in terms of “limited” or “readily”. However, for a given compound, the rate and extent of BBB transport will be the net result of the contribution of many possible passive and active dynamically regulated transport mechanisms. This implies that knowledge of BBB transport mechanisms and regulation is critical for the understanding of brain homeostasis; on one hand to gain insights into how disturbances thereof may lead to CNS diseases, and on the other hand to ultimate being able to predict the relation between the kinetics and the dynamics of CNS active compounds. Among a number of in vivo techniques to study BBB transport, in vivo microdialysis has the important unique characteristic to provide data on free concentrations in the extracellular (EC) spaces in the body. This characteristic makes microdialysis especially valuable as a technique to study the kinetics of BBB membrane transport. In this chapter, the focus is on the use of intracerebral microdialysis technique to study BBB transport and (within) brain distribution. A total of 282 references are used. Following introduction, in II, the determinants in BBB functionality are presented with circumstances that affect BBB functionality. Then, part III deals with in vivo techniques to study BBB transport, including microdialysis. Subsequently part IV presents crucial methodological factors that determine the validity of microdialysis outcomes, approaches in pharmacokinetic modelling of BBB transport using microdialysis, brain tissue and plasma/blood data. Then, in V, the currently available reviews on BBB transport studies with microdialysis are presented, followed by the more recent original papers dealing with passive and active BBB transport mechanisms, as well as potential changes thereof in a number of disease conditions. Finally (VI), it is concluded that the use of microdialysis combined with brain tissue and plasma/blood data provides a good approach in characterising BBB transport mechanisms in many species, under a variety of conditions.