Implications of the Blood-Brain Barrier and Its Manipulation

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.