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 doin g so for the first time, choosing a method can be a formidable task. T here 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 advan tages and disadvantages. Some methods require very little equipment wh ile others require equipment that can cost millions of dollars. Some m ethods 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 dif ferential equations. Like most things in science, as the complexity of the technique increases, so does the quantity of information it provi des. This review is meant to serve as a starting point for the researc her who wishes to study transport and uptake across the blood-brain ba rrier in animal models. An overview of the mathematical theory, as wel l as an introduction to the techniques, is presented.