Animal models for studying transport across the blood-brain barrier

There are many reasons for wishing to determine the rate of uptake of a drug from blood into brain parenchyma. However, when faced with doing so for the first time, choosing a method can be a formidable task. There are at least 7 methods from which to choose: indicator dilution, brain uptake index, microdialysis, external registration, PET scanning, in situ perfusion, and compartmental modeling. Each method has advantages and disadvantages. Some methods require very little equipment while others require equipment that can cost millions of dollars. Some methods require very little technical experience whereas others require complex surgical manipulation. The mathematics alone for the various methods range from simple algebra to complex integral calculus and differential equations. Like most things in science, as the complexity of the technique increases, so does the quantity of information it provides. This review is meant to serve as a starting point for the researcher who wishes to study transport and uptake across the blood-brain barrier in animal models. An overview of the mathematical theory, as well as an introduction to the techniques, is presented.