The blood-brain barrier is still not completely understood and therefore the subject of fascinating study. How are endogenous substances transported through the blood-brain barrier? What are the known therapeutic and toxic agents? How are they transported across cerebral microvessels? The discussion of these and other questions with far-reaching consequences for all neuroscientists can be found in this volume. This authoritative and up-to-date review of the blood-brain barrier gives a proper understanding of the topic. The experimental principles, the results of very recent research, as well as the implications that experimental research has for clinical treatment are thoroughly covered. Information is given on: - new findings based on classical physiological and pharmacological techniques, - results obtained from brain capillaries in vitro and in culture, - results obtained from the new scanning techniques (PET and MRI), - the immunology of the blood-brain barrier, - trace metal transport, - the pathological breakdown of the barrier and - the modification of drugs to increase their entry into the brain. Here is a source of information that is invaluable to specialists concerned with basic research in the neurosciences, with the design of neuropharmacological agents, with the radiological diagnosis of cerebral pathology or with the treatment of cerebral lesions!
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1 Ultrastructure of Brain Endothelium.- A. Endothelium as a Blood-Brain Barrier.- B. Astroglia as a Blood-Brain Barrier.- C. Blood-Brain Access.- I. Vascularization of Grafts to the Brain.- 1. Grafts of Peripheral Tissues.- 2. Similarity Between Ventricle and Anterior Chamber of the Eye.- 3. CNS Versus Peripheral Tissue Grafts.- II. Immunological Aspects of the Endothelium.- III. Circumventricular Organs.- 1. Fenestrae.- 2. Pits and Vesicles.- 3. Tubules.- D. Ontogeny.- E. Astrocytic Modulation of the Barrier.- F. Constituents of Barrier Cell Membranes.- References.- 2 Methods of Study.- A. Introduction.- B. Morphologic Techniques.- I. Organic Dye Tracers.- II. Electron Microscopy.- III. Quantitative Morphometry.- C. In Vivo Transport Methods.- I. Intravenous Administration/Compartmental Analysis.- II. Brain Perfusion.- III. Indicator Dilution.- IV. Brain Uptake Index.- V. Other Techniques.- D. New Dimensions.- I. Evaluation of Barrier Transport and Permeability in Humans.- 1. Positron Emission Tomography.- 2. Magnetic Resonance Imaging.- II. Autoradiography.- III. Brain Vasculature/Perfused Capillaries.- IV. Other Barrier Sites.- 1. Choroid Plexus Epithelium.- 2. Blood-Nerve Barrier.- 3. Blood-Retinal Barrier.- V. In Vivo Microdialysis.- VI. Single Capillary Studies.- E. Molecular/Cellular Biology.- I. Isolated Microvessels/Endothelial Monolayers.- II. Identification of Barrier Transporters and Enzymes.- III. Expression of Barrier Characteristics.- F. Summary and Perspectives.- References.- 3 Diffusional and Osmotic Permeability to Water.- A. Introduction.- B. The Nature of Permeability.- C. Water Permeability of the Blood-Brain Barrier.- I. Diffusive Permeability.- II. Osmotic Permeability.- D. Conclusion.- References.- 4 Blood-Brain Glucose Transfer.- A. Brief History.- B. Brain Endothelial Glucose Transporter.- I. Molecular Biology.- II. Molecular Kinetics.- III. Structural Requirements of Glucose Transport.- C. Theory of Blood-Brain Glucose Transfer.- I. Apparent Permeability and Flux.- II. Facilitated Diffusion.- 1. Michaelis-Menten Equation.- 2. Michaelis-Menten Constants.- 3. Partition Volume.- III. Multiple Membranes.- 1. Endothelial Membranes.- 2. Glial and Neuronal Cell Membranes.- D. Evidence of Blood-Brain Glucose Transfer.- I. Methods.- 1. Operational Equations.- 2. Experimental Procedures.- 3. The Blood-Brain Barrier In Vitro.- II. Normal Values in Awake Subjects.- 1. Permeability and Flux in Normoglycemia.- 2. Michaelis-Menten Constants.- 3. Non-Saturable Glucose Transfer.- 4. Metabolism-Flux Ratio and the Lumped Constant.- III. Acute Changes of Glucose Transport.- 1. Activation and Deactivation.- 2. Carbon Dioxide and Spreading Depression.- 3. Anoxia and Ischaemia.- IV. Chronic Changes.- 1. Pre- and Postnatal Development.- 2. Dementia.- 3. Hypo- and Hyperglycaemia.- References.- 5 Transport of Amino Acids.- A. Amino Acid Transport Systems in Animal Cells.- B. Neutral and Cationic Amino Acids.- I. Influx.- 1. Quantification of Influx.- 2. Summary of the Results Obtained.- II. Efflux.- 1. Efflux in the Capillaries.- 2. Passive Efflux Via the Arachnoid Villi.- 3. Efflux Via the Choroid Plexus and Arachnoid Membrane.- III. Net Uptake.- C. Anionic Amino Acids.- D. Metabolism in the Endothelial Cells of Some Transported Amino Acids.- E. Regulation of Blood-Brain Amino Acid Transport.- I. Availability of Amino Acids: Plasma Amino Acid Concentration.- II. Proportions and Rate of Transport of the Amino Acids Between Blood and Brain.- III. Is Amino Acid Transport Modified by Hormones?.- IV. Can Amino Acid Transport Be Modified by Neurotransmitters?.- F. Physiological and Pathological Modifications.- I. Blood-Brain Amino Acid Transport During Development.- 1. Technical Problems.- 2. How Many Blood-Brain Transport Systems Have Been Found in Immature Animals?.- 3. Coexistence of Higher Blood-Brain Transport with a Lower Density of Capillaries.- 4. When Does the Asymmetry of Transport Between the Two Membranes of the Endothelial Cells Appear?.- II. Effect of Drugs on Blood-Brain Transport of Amino Acids.- III. Pathological Modifications of Amino Acid Transport.- 1. Hepatic Encephalopathies.- 2. Uraemia.- 3. Diabetes.- 4. Aminoaciduria.- 5. Intoxications.- 6. Depressive States.- References.- 6 Peptides and the Blood-Brain Barrier.- A. Introduction: Central Actions of Peripherally Administered Peptides.- B. Uptake of Peptides at the Blood-Brain Interfaces.- I. Intracarotid Bolus Injection Studies (Brain Uptake Index).- II. Intravenous Bolus Injection Studies.- III. Brain Perfusion Studies.- IV. Choroid Plexus Perfusion Studies.- V. Isolated Cerebral Microvessels.- VI. Cultured Cerebral Endothelial Cells.- C. Evidence for Transport Into Brain Extracellular Fluid.- D. The Influence of Peptides on Blood-Brain Barrier Permeability to Specific Solutes.- E. General Conclusions.- References.- 7 The Movement of Vitamins Into the Brain.- A. Routes.- I. The Trans-Capillary Route.- II. Other Possible Routes.- B. Mechanisms.- I. Passive Diffusion.- II. Carrier-Mediated Transport.- III. Binding Proteins.- IV. Covalently Bound Carriers.- C. The Individual Vitamins.- I. Thiamine.- II. Ascorbic Acid.- III. Pyridoxine.- IV. Folates.- V. Vitamin B12.- VI. Nicotinamide, Nicotinic Acid.- VII. Choline.- VIII. Nucleosides and Purine Bases.- IX. Other B-Vitamins.- X. Lipophilic Vitamins.- D. Clinical Implications.- E. Homeostasis.- F. Conclusions.- References.- 8 Electrolyte Transport.- A. Brain Electrolyte Homeostasis.- I. Stability of the Extracellular Potassium Concentration.- II. Spatial Buffering of Potassium.- III. Extracellular Sodium and Chloride Concentrations.- IV. Pathologic Conditions.- B. Blood-Brain Barrier Permeability to Electrolytes.- I. Measurements of Electrolyte Permeability.- II. Route of Electrolyte Passage Across the BBB.- 1. Passive Permeability Pathways.- 2. Evidence for Active Transport Pathways.- III. Epithelial Properties of the Brain Capillary Endothelium.- IV. Mechanisms of Ion Transport Across the BBB.- 1. Luminal Entry Mechanisms.- 2. Abluminal Transport Systems.- V. Regulation of BBB Permeability to Ions.- 1. Regulation by Electrolytes and Glucose.- 2. Regulation by Nerves.- 3. Regulation by Hormones.- References.- 9 Secretion and Bulk Flow of Interstitial Fluid.- A. Introduction.- B. Factors Governing Extracellular Fluid Exchanges Within the Brain.- I. Blood-Brain Barrier.- II. Cerebral ISF and CSF.- III. Pathways of Flow Between Brain and CSF.- C. Bulk Flow of ISF.- I. Methods of Study.- II. Drainage of ISF from Brain to CSF.- 1. Historical Perspectives.- 2…