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Springer Implications of the Blood-Brain Barrier and Its Manipulation Volume 1 Basic Science Aspects 1st Editon 2011 Softbound by E.A. Neuwelt
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. 1. The Challenge of the Blood-Brain Barrier.- 1. Introduction.- 2. Do Monocytes Stream across the Blood-Brain Barrier in Response to Brain Injury?.- 3. Effects of Injury to the Blood-Brain Barrier by Mass Lesions in the CNS: Neuroradiologic Characteristics.- 4. Encephalopathy Associated with Cryoprecipitable Australia Antigen.- 5. Adoptive Immunotherapy as a Means to Circumvent the Blood-Brain Barrier and the Immunologic Privilege of the CNS.- 6. The Dramatic Effect of Corticosteroids on Vasogenic Cerebral Edema.- 7. The Role of Blood-Brain Barrier Modification in the Treatment of Primary Brain Tumors.- 8. Competition at the Blood-Brain Barrier by Dietary Amino Acids Causing Fluctuations in the Motor Performance of Patients with Parkinson Disease Who Are Receiving Levodopa Therapy.- 9. Conclusion.- References.- 2. History of the Blood-Brain Barrier Concept.- 1. Studies with Dyestuffs.- 2. The Stern-Gautier Hypothesis.- 3. Selectivity of the Barrier.- 4. Lipid Solubility.- 5. Sink Action of the Cerebrospinal Fluid.- 6. Morphology of the Blood-Brain Barrier.- 6.1. Brain Capillary Endothelial Cell End-Feet.- 6.2. Electron Microscopists’ Heresy.- 7. The Extracellular Space of the Brain.- 8. The Barriers and Homeostasis.- 8.1. Brain Extracellular Fluid.- 8.2. Cerebral Edema.- 9. Ontogeny of the Blood-Brain Barrier.- 9.1. Rate of Protein Exchange.- 9.2. Concentrations of Individual Proteins.- 10. Comparative Aspects.- 10.1. Elasmobranchs.- 10.2. Holocephalans.- 10.3. Cyclostomes.- 10.4. The Invertebrate Barrier.- 10.5. Value of Comparative Studies.- 11. The Present Era.- 11.1. Perfused Brain.- 11.2. Isolated Choroid Plexus.- 11.3. Isolated Brain Microvessels.- 12. Summary.- References.- 3. The Anatomic Basis of the Blood-Brain Barrier.- 1. Intercellular Tight Junctions.- 1.1. Structure and Permeability.- 1.2. Glial Modulation.- 2. Pits, Vesicles, and Channels.- 2.1. Vesicle Translocation.- 2.2. Most Vesicles May Be Pits.- 2.3. Vesicle Fusion and Fission.- 2.4. Cryofixation and Chemical Fixation.- 3. Receptors.- 3.1. Insulin.- 3.2. Low-Density Lipoprotein.- 3.3. Transferrin.- 4. Electric Charge.- 4.1. Charge and Endocytosis.- 4.2. Charge and Lectin Binding.- 5. Circumventing the Barrier.- 5.1. Retrograde Axonal Transport.- 5.2. Endothelial Alteration.- 5.3. Transplants.- 6. Extravascular Spread of Peroxidase.- 6.1. Perivascular Basement Membrane.- 6.2. Interstitial Compartment.- 6.3. Clearance via Basement Membranes.- 7. Enzymes.- 8. Conclusions.- References.- 4. Quantitation of Blood-Brain Barrier Permeability.- 1. Introduction.- 2. Two Methodologic Approaches.- 3. Continuous Uptake.- 3.1. Intravenous Administration.- 3.2. Brain-Perfusion Technique.- 4. Single-Pass Uptake.- 4.1. Indicator Diffusion.- 4.2. Brain Uptake Index.- 4.3. Single Injection-External Registration.- 5. Summary.- References.- 5. Transport across the Blood-Brain Barrier.- 1. Physicochemical Factors Influencing Permeability.- 1.1. Solute Transport.- 1.2. Water.- 1.3. Influence of Protein Binding.- 1.4. Convection in Cerebral Interstitial Fluid.- 2. Specific Transport.- 2.1. Monosaccharides.- 2.2. Monocarboxylic Acids.- 2.3. Amino Acids.- 2.4. Vitamins, Cofactors, and Nucleic Acid Precursors.- 2.5. Peptides.- 3. Factors Modifying Permeability.- 3.1. Blood Flow and Permeability.- 3.2. Modulation of Transport Mechanisms.- 4. Conclusions.- References.- 6. Pharmacology of the Blood-Brain Barrier.- 1. Introduction.- 2. Methods of Measuring Drug Transfer.- 3. Capillary Transport Models and PS Products.- 4. Mechanisms of Transport to and through the BBB.- 5. Local Differences in Influx.- 6. Drug Permeability and Distribution.- 7. Summary.- References.- 7. Ontogeny and Phytogeny of the Blood-Brain Barrier.- 1. Introduction.- 2. Ontogenetic and Phylogenetic Animal Models of Barriers.- 3. Structural Configurations of Barrier Systems in Infant Mammals.- 3.1. Blood-Brain Barrier