As a neurologist and student of the microvasculature, I find great pleasure in introducing this treatise. Presented here is a view of brain pathophysiology and therapy from the perspective of the blood-brain barrier (BBB). Virtually every disease process that affects the brain-traumatic, neoplastic, infectious, inflammatory, toxic, metabolic, degenera tive, vascular, and epileptic-affects the BBB. Damage to this homeostatic system often leads to disruption of the composition and volume of brain fluid compartments, thereby contributing to neurologic symptoms and pathology. Furthermore, in disorders in which the integrity of the barrier is not breached, its normal restrictive nature may limit therapeu tic approaches. For example, the barrier appears to function normally in Parkinson dis ease, but its ability to compensate for striatal dopamine depletion is in part determined by the activity of transporters and enzymes operative in the brain microvasculature. of antibiotics, anticonvulsants, antineoplastic agents, and neurolep Similarly, the choice tics requires attention to these drugs' interaction with the BBB. Thus, the barrier inter faces with virtually all nervous system diseases and therapies. Future brain treatments with regulatory peptides, immune mediators, and gene components will require selective methods to deliver these agents to specific brain regions. The second volume of this text successfully provides a thorough review of BBB function and failure in a variety of clinical situations.

Understanding the structure and function of the blood-brain barrier (BBB) and recogniz ing its clinical relevance require a concert of scientific disciplines applied from a view point of integrative physiology rather than from only molecular or analytical approaches. It is this broad scope that is emphasized in this book. In my opinion, four original contributions define the field as it exists today. The first, a monograph by Broman,1 entitled The Permeability of the Cerebrospinal Vessels in Normal and Pathological Conditions, was the model for many subsequent clinical and 3 experimental studies on BBB pathology. Second, experiments by Davson, summarized in his book entitled Physiology of the Ocular and Cerebrospinal Fluids, indicated that passive entry of nonelectrolytes into brain from blood is governed largely by their lipid 4 solubility. This research supported the original suggestion by Gesell and Hertzman that cerebral membranes have the semipermeability properties of cell membranes. The modem era of the barrier was introduced with the 1965 paper by Crone,2 entitled "Facilitated transfer of glucose from blood to brain tissue. " This paper identified stereospecific, facilitated transport of glucose as part of a system of regulatory barrier properties at a time when only a barrier to passive diffusion had been contemplated. Finally, the 1967 paper by Reese and Kamovsky, 11 entitled "Fine structural localization of a blood-brain barrier to exogenous peroxidase," sited the barrier at the continuous layer of cerebrovascular endothelial cells, which are connected by tight junctions.