Frontiers in Cerebral Vascular Biology: Transport and Its Regulation (Advances in Experimental Medicine and Biology, 331)

During the past three decades, the cerebral vasculature and its role in blood-brain transport has been an increasingly active area of investigation and learning, particularly from an anatomical and physiological point of view. However, much less is known at the molecular and cellular level about the blood-brain barrier especially regarding the macromolecules responsible for transport, the roles played by vascular wall components (endothelial cell, pericyte, smooth muscle, basement membrane), and the mechanisms regulating brain vascular-specific protein expression and their molecular alterations during development and disease. Fundamental questions still unanswered include: What are the molecular constituents of brain endothelial cell tight junctions? What are the membrane proteins responsible for transport of specific substrates? What are the molecular signals that cause glucose transporter gene expression to be 20 to 100 times greater in brain endothelial cells in vivo than in vitro? What roles do pericytes, smooth muscle cells and basement membrane have in establishing or maintaining blood-brain transport characteristics? Are brain vascular transport systems responsible for edema following injury? Are transporter systems regulated via receptor-mediated events? Do hormones or neuromodulators regulate transporter expression? What is the molecular mechanism by which plasma proteins enter the extravascular space? Are transporters asymmetrically distributed between the luminal and abluminal endothelial cell membranes? Can prodrugs or pharmacologic agents be designed as substrate analogs and be delivered to the central nervous system via existing transporters or receptors? Can new and beneficial transporters be introduced into the brain vasculature? Front Matter....Pages i-x Front Matter....Pages 1-1 Developmental Expression of Glucose Transporters, Glut1 and Glut3, in Postnatal Rat Brain....Pages 3-7 Alterations in Brain Glucose Transporter Proteins, Glut1 and Glut3, in Streptozotocin Diabetic Rats....Pages 9-12 Glucose Transporter (Glut1) Expression by Canine Brain Microvessel Endothelial Cells in Culture: An Immunocytochemical Study....Pages 13-18 Application of Novel PCR Strategies to Amplify and Sequence Glucose Transporters in Canine Brain....Pages 19-24 Estimation of Unidirectional Clearances of FDG and Glucose Across the Blood-Brain Barrier in Man....Pages 25-27 Rat Brain Glucose Concentration and Transport Kinetics Determined with 13 C Nuclear Magnetic Resonance Spectroscopy....Pages 29-34 Non-Invasive Measurements of the Cerebral Steady-State Glucose Concentration and Transport in Humans by 13 C Nuclear Magnetic Resonance....Pages 35-40 Front Matter....Pages 41-41 Potassium Transport at the Blood-Brain and Blood-CSF Barriers....Pages 43-54 Expression of Na, K-ATPase at the Blood-Brain Interface....Pages 55-60 Effects of Protein Kinase C Agonists on Na, K-ATPase Activity in Rat Brain Microvessels....Pages 61-64 Brain Volume Regulation During Development: The Role of Blood-Brain Barrier Potassium Transport....Pages 65-69 The Transendothelial DC Potential of Rat Blood-Brain Barrier Vessels in Situ....Pages 71-74 Phosphate Transport in Capillaries of the Blood-Brain Barrier....Pages 75-80 Front Matter....Pages 81-81 Drug Delivery to Brain and the Role of Carrier-Mediated Transport....Pages 83-93 Vasopressin Modulates the Blood-Brain Transfer of Amino Acids-Studies with [ 11 C]Methionine in Dogs....Pages 95-100 Amino Acid Transport at the Blood-Nerve Barrier of the Rat Peripheral Nerve....Pages 101-106 Effect of Intra-Uterine Growth Retardation on Cerebral Amino Acid Transport from Birth to Adulthood....Pages 107-111 Drug Transfer Across the Blood-Brain Barrier: Comparison of in Vitro and in Vivo Models....Pages 113-115 Differential Brain Penetration of Cerebroprotective Drugs....Pages 117-120 P-Glycoprotein is Strongly Expressed in Brain Capillaries....Pages 121-125 Front Matter....Pages 127-127 Transport of Proteins Across the Blood-Brain Barrier via the Transferrin Receptor....Pages 129-136 Endothelial Cell Biology and the Enigma of Transcytosis Through the Blood-Brain Barrier....Pages 137-141 Blood-Brain Transport of Vasopressin....Pages 143-147 Cerebral Pericytes — A Second Line of Defense in Controlling Blood-Brain Barrier Peptide Metabolism....Pages 149-152 Front Matter....Pages 153-153 The Role of Second Messenger Molecules in the Regulation of Permeability in the Cerebral Endothelial Cells....Pages 155-164 Peptidergic Induction of Endothelin 1 and Prostanoid Secretion in Human Cerebromicrovascular Endothelium....Pages 165-170 Endothelin-1 Binding to Human Brain Microvascular and Capillary Endothelium: Membranes vs. Intact Cells....Pages 171-176 Possible Involvement of C-Kinase in Occurrence of Chronic Cerebral Vasospasm after Subarachnoid Hemorrhage....Pages 177-182 A Novel Gene Family May Encode Endothelial Cell Specific Adhesion-Like Molecules: An Extracellular Loop-Repeat-Loop (LRL) Motif and Cytoplasmic Tyrosine Kinase Domains....Pages 183-185 Front Matter....Pages 187-187 Plasminogen Activation and Astroglial-Induced Neural Microvessel Morphogenesis....Pages 189-199 Immortalized Rat Brain Microvessel Endothelial Cells: I - Expression of Blood-Brain Barrier Markers During Angiogenesis....Pages 201-204 Immortalized Rat Brain Microvessel Endothelial Cells: II-Pharmacological Characterization....Pages 205-210 Expression of the HT7 Gene in Blood-Brain Barrier....Pages 211-215 Astrocytes Secrete a Factor Inducing the Expression of HT7-Protein and Neurothelin in Endothelial Cells of Chorioallantoic Vessels....Pages 217-221 Chorioallantoic Membrane (CAM) Vessels do not Respond to Blood-Brain Barrier (BBB) Induction....Pages 223-228 Cerebral Endothelium and Astrocytes Cooperate in Supplying Docosahexaenoic Acid to Neurons....Pages 229-233 Front Matter....Pages 235-235 Effect of Cytokines on ICAM Expression and T Cell Adhesion to Cerebrovascular Endothelial Cells....Pages 237-242 Expression of Endothelial Cell Activation Antigens in Microvessels from Patients with Multiple Sclerosis....Pages 243-248 Generation of an Anti-Mouse Brain Endothelial Cell Monoclonal Antibody that Recognizes 84-110 kDa and 36 kDa Determinants that are Upregulated by Cytokines....Pages 249-254 Front Matter....Pages 255-255 The Use of Intracerebral Microdialysis to Study Blood-Brain Barrier Transport in Health, After Modification and in Disease....Pages 257-262 Front Matter....Pages 255-255 Cerebral Endothelial Mechanisms in Increased Permeability in Chronic Hypertension....Pages 263-266 Altered Fatty Acid Composition of Ethanolamine Phosphoglyceride in Brain Microvessels from Senescent Mouse....Pages 267-271 Preirradiation Osmotic Blood-Brain Barrier Disruption Plus Combination Chemotherapy in Gliomas: Quantitation of Tumor Response to Assess Chemosensitivity....Pages 273-284 The Uptake of Thyroxine by the Isolated Perfused Choroid Plexus of the Sheep....Pages 285-288 Back Matter....Pages 289-295