Implications Of The Blood Brain Barrier And Its Manipulation

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.

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.

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.

The blood-brain barrier serves to protect the brain from toxic substances whilst simultaneously allowing access to essential nutrients and chemical signals. At the interface between brain and body, knowledge of the blood-brain barrier forms an essential component in the complete understanding of a large proportion of medical disciplines. Nevertheless, it seems that ignorance of both the biology of this important membrane and the methodology suitable for its investigation still remains an impediment to progress in many fields, including, for example, the development of new and efficacious neuropharmaceuticals, cerebrovascular disease, Alzheimer's disease, cerebral AIDS and brain tumours. This introduction for both researchers and clinicians across the medical sciences is intended to aid both those beginning work directly in this area and those wishing simply to be better informed when interpreting information where the blood-brain barrier may be involved. Advances in both methodology and biology are detailed in 50 chapters from international authorities.

Proceedings of the Cerebral Vascular Biology Symposium held in Paris, France, July 10-12, 1995

The blood-brain barrier, a concept including all morphological and functional mechanisms that restricts or facilitates the passage of substances from blood to brain, enables the brain environment to be regulated relatively independently from concentration and fluctuations in plasma constituents. The various aspects on the blood-brain barrier have been extensively discussed in a number of recent symposia and our knowledge on the blood-brain barrier physiology has advanced impressively during the last decade. However, as to the pathophysiology and the long-term consequences of a transient or permanent barrier damage, little is known - a fact attributable to the limited amount of interest shown in this area of research until recently. The idea to arrange a Fernstrom symposium on the consequences of barrier damage emerged in 1987, when findings in Barbro Johansson's Laboratory of Experimental Neurology indicated that opening of the blood-brain barrier in various experimental models could lead to permanent neuronal injury."