1 Introduction --; 2 Methods for the study of the functions of the blood-brain barrier --; 3 Amino acids and the blood-brain barrier --; 4 The role of peptides in the brain --; 5 Brain peptides and peptidergic pathways --; 6 The interaction of small peptides with the various cellular interfaces of the blood-brain barrier --; 7 Transport of large peptides and proteins across the blood-brain barrier --; 8 Disease states and the blood-brain barrier related to peptides --; 9 Immunological and other aspects of the blood-brain barrier --; 10 Strategies for peptide delivery to the brain.
Definition of the barrier The interstitial fluid (rSF) of the brain is separated from the blood by the blood-brain barrier (BBB). This barrier must not be thought of as a single entity or as an absolute restriction to all molecules, but as a multiple structure located at several sites within the brain. The first of these interfaces is located at the endothelium of the brain capillaries. Secondly there is a potential site for interchange on the outer linings of the brain between the dura and the arachnoid membranes. Thirdly, there are the choroid plexuses and the cerebrospinal fluid (CSF) which is in contact with the very permeable internal ependymal lining of the brain (Figure 1. 1). Finally there are areas of the brain which lack a blood-brain barrier. These areas constitute the circumventricu lar organs and have leaky capillaries with a barrier at the ependyma which limits the spread of molecules from those regions (Figure 1. 2). Each of these BBB sites has its own characteristic permeability and transport functions. We will now consider the properties of each of these barrier sites between the blood and the brain. THE CEREBRAL CAPILLARY ENDOTHELIUM Morphology This interface has both the largest surface area and the shortest path length between the blood and the brain rSF. The cerebral capillaries, which at first sight seem little different from the rest of the systemic circulation, are in fact unique to the brain.