Blood–Brain Barriers – From Ontogeny to Artificial Interfaces 2VST

Rolf Dermietzel is Professor and head of the Department of Neuroanatomy and Molecular Brain Research at the Ruhr University in Bochum, Germany. He gained his PhD from the University Hospital in Essen, Germany, in 1970, before training in cell biology at the California Institute of Technology and the Marine Biological Institute in Woods Hole, MA. His research focuses on identifying the molecular make-up of the blood-brain barrier and the role of gap junctions in brain tissues. Professor Dermietzel has won several awards in electron microscopy, and co-authored three books in different fields of neurosciences, among them the bestselling Handbook of Neurotransmitters and Neuromodulators. David C. Spray is Professor of Neuroscience and Medicine (Cardiology) at the Albert Einstein College of Medicine, NY. He obtained his PhD from the University of Florida College of Medicine in 1973, and is also Adjunct Professor of Biomedical Engineering at City College. His research has focused on physiological roles of gap junction channels, how alterations in gap junction expression and function lead to disease and whether novel types of gap junction-altering drugs may be therapeutically useful. Professor Spray is a foreign member of the Brazilian Academy of Sciences and has published some 350 full-length papers and book chapters. Maiken Nedergaard received an M.D. from the University of Copenhagen, Denmark, in 1983, and her Ph.D. from the University of Copenhagen in 1988. She worked at Cornell University Medical College before joining the faculty of New York Medical College as Professor of Cell Biology in 1994. Since 2003 she has been on the faculty of the University of Rochester. Her work focuses on defining the role of astrocytes in synaptic plasticity, as well as in acute neurological diseases, including stroke, spinal cord injury and epilepsy. Recently Professor Nedergaard has been analyzing the significance of glutamatergic signaling in malignant gliomas.

Preface.List of Contributors.VOLUME 1.Introduction.The Blood-Brain Barrier: An Integrated Concept (Rolf Dermietzel, David C. Spray, and Maiken Nedergaard).Part I Ontogeny of the Blood-Brain Barrier.1 Development of the Blood-Brain Interface (Britta Engelhardt).1.1 Introduction.1.2 Pioneering Research on the Blood-Brain Barrier.1.3 The Mature Blood-Brain Interface.1.4 Development of the CNS Vasculature.1.5 Differentiation of the Blood-Brain Barrier.1.6 Maintenance of the Blood-Brain Barrier.1.7 Outlook.2 Brain Angiogenesis and Barriergenesis (Jeong Ae Park, Yoon Kyung Choi, Sae-Won Kim,and Kyu-Won Kim).2.1 Introduction.2.2 Brain Angiogenesis.2.3 Oxygenation in the Brain: Brain Barriergenesis.2.4 Perspectives.3 Microvascular Influences on Progenitor Cell Mobilization and Fate in the Adult Brain (Christina Lilliehook and Steven A. Goldman).3.1 Introduction.3.2 Angiogenic Foci Persist in the Adult Brain.3.3 Neurotrophic Cytokines Can Be of Vascular Origin.3.4 Angiogenesis and Neurogenesis are Linked in the Adult Avian Brain.3.5 Angiogenesis-Neurogenesis Interactions in the Adult Mammalian Brain.3.6 Purinergic Signaling to Neural Progenitors Cells: the Gliovascular Unit as a Functional Entity.3.7 Nitric Oxide is a Local Modulator of Progenitor Cell Mobilization.3.8 Parenchymal Neural Progenitor Cells May Reside Among Microvascular Pericytes.3.9 The Role of the Vasculature in Post-Ischemic Mobilization of Progenitor Cells.Part II The Cells of the Blood-Brain Interface. 4 The Endothelial Frontier (Hartwig Wolburg).4.1 Introduction.4.2 The Brain Capillary Endothelial Cell.4.3 Endothelial Structures Regulating Transendothelial Permeability.4.4 Brief Consideration of the Neuroglio-Vascular Complex.4.5 Conclusions.5 Pericytes and Their Contribution to the Blood-Brain Barrier (Markus Ramsauer).5.1 Introduction.5.2 Pericyte Structure and Positioning.5.3 Pericyte Markers.5.4 Pericytes in Culture.5.5 Contractility and Regulation of Blood Flow.5.6 Macrophage Function.5.7 Regulation of Homeostasis and Integrity.5.8 Angiogenesis and Stability.5.9 Conclusion.6 Brain Macrophages: Enigmas and Conundrums (Frederic Mercier, Sebastien Mambie, and Glenn I. Hatton).6.1 Introduction.6.2 Different Types and Locations of Brain Macrophages.6.3 Migration of Brain Macrophages.6.4 Fast Renewal of Brain Macrophages.6.5 Functions.6.6 Conclusion: Macrophages as Architects of the CNS Throughout Adulthood.7 The Microglial Component (Ingo Bechmann, Angelika Rappert, Josef Priller, and Robert Nitsch).7.1 Microglia: Intrinsic Immune Sensor Cells of the CNS.7.2 Terminology: Subtypes and Their Location in Regard to Brain Vessels.7.3 Turnover of Brain Mononuclear Cells by Precursor Recruitment Across the BBB.7.4 Microglial Impact on BBB Function.7.5 Concluding Remarks.8 The Bipolar Astrocyte: Polarized Features of Astrocytic Glia Underlying Physiology, with Particular Reference to the Blood-Brain Barrier (N. Joan Abbott).8.1 Introduction.8.2 Formation of the Neural Tube.8.3 Origin of Neurons and Glia.8.4 Morphology of Glial Polarity in Adult CNS.8.5 Astrocyte Spacing and Boundary Layers.8.6 Origin and Molecular Basis of Cell Polarity.8.7 Functional Polarity of Astrocytes and Other Ependymoglial Derivatives.8.8 Secretory Functions of Astrocytes.8.9 Induction of BBB Properties in Brain Endothelium.8.10 Astrocyte-Endothelial Signaling.8.11 Conclusion.9 Responsive Astrocytic Endfeet: the Role of AQP4 in BBB Development and Functioning (Grazia P. Nicchia, Beatrice Nico, Laura M.A. Camassa,Maria G. Mola, Domenico Ribatti, David C. Spray, Alejandra Bosco,Maria Svelto, and Antonio Frigeri).9.1 Introduction.9.2 Astrocyte Endfeet and BBB Maintenance.9.3 Astrocyte Endfeet and BBB Development.9.4 Astrocyte Endfeet and BBB Damage.9.5 The Role of Aquaporins in BBB Maintenance and Brain Edema.9.6 AQP4 Expression in Astrocyte-Endothelial Cocultures.Part III Hormonal and Enzymatic Control of Brain Vessels.10 The Role of Fibroblast Growth Factor 2 in the Establishment and Maintenance of the Blood-Brain Barrier (Bernhard Reuss).10.1 Introduction.10.2 Role of FGF-2 in the Regulation of BBB Formation.10.3 Future Perspectives.11 Cytokines Interact with the Blood-Brain Barrier (Weihong Pan, Shulin Xiang, Hong Tu, and Abba J. Kastin).11.1 Introduction.11.2 Identification of the Phenomena.11.3 Mechanisms of Cytokine Interactions with the BBB.11.4 Regulation of the Interactions of Cytokines with the BBB.11.5 Stroke and Other Vasculopathy.11.6 Neurodegenerative Disorders.11.7 Summary.12 Insulin and the Blood-Brain Barrier (William A. Banks and Wee Shiong Lim).12.1 Introduction.12.2 Pathophysiology of Insulin Transport.13 Glucocorticoid Hormones and Estrogens: Their Interaction with the Endothelial Cells of the Blood-Brain Barrier (Jean-Bernard Dietrich).13.1 Introduction.13.2 Glucocorticoids and the Endothelial Cells of the BBB.13.3 Estrogens and the Endothelial Cells of the BBB.13.4 Conclusions and Perspectives.14 Metalloproteinases and the Brain Microvasculature (Dorothee Krause and Christina Lohmann).14.1 Introduction.14.2 Metalloproteinases in Brain Microvessels: Types and Functions.14.3 Cerebral Endothelial Cells and Metalloproteinases.14.4 Perivascular Cells and Metalloproteinases.14.5 Metalloproteinases and the Blood-Liquor Barrier.14.6 Metalloproteinases and Brain Diseases.14.7 Conclusion.Part IV Culturing the Blood-Brain Barrier.15 Modeling the Blood-Brain Barrier (Romeo Cecchelli, Caroline Coisne, Lucie Dehouck, Florence Miller, Marie-Pierre Dehouck, Valerie Buee-Scherrer, and Benedicte Dehouck).15.1 Introduction.15.2 Culturing Brain Capillary Endothelial Cells.15.3 Characteristics Required for a Useful In Vitro BBB Model.15.4 Conclusion.16 Induction of Blood-Brain Barrier Properties in Cultured Endothelial Cells (Alla Zozulya, Christian Weidenfeller, and Hans-Joachim Galla).16.1 Introduction.16.2 In Vitro BBB Models.16.3 Hydrocortisone Reinforces the Barrier Properties of Primary Cultured Cerebral Endothelial Cells.16.4 The Involvement of Serum Effects.16.5 Hydrocortisone Improves the Culture Substrate by Suppressing the Expression of Matrix Metalloproteinases In Vitro.16.6 The Role of Endogenously Derived ECM for the BBB Properties of Cerebral Endothelial Cells In Vitro 368 16.7 Conclusions.17 Artificial Blood-Brain Barriers (Luca Cucullo, Emily Oby, Kerri Hallene, Barbara Aumayr, Ed Rapp, and Damir Janigro).17.1 Introduction: The Blood-Brain Barrier.17.2 Requirements for a Good BBB Model.17.3 Immobilized Artificial Membranes.17.4 Cell Culture-Based in vitro BBB Models.17.5 Shear Stress and Cell Differentiation.17.6 Flow-Based in vitro BBB Systems.17.7 A Look Into The Future: Automated Flow Based in vitro BBBs.17.8 Conclusion.18 In Silico Prediction Models for Blood-Brain Barrier Permeation (Gerhard F. Ecker and Christian R. Noe).18.1 Introduction: The In Silico World.18.2 The Blood-Brain Barrier.18.3 Data Sets Available.18.4 Computational Models.18.5 Passive Diffusion.18.6 Field-Based Methods.18.7 Active Transport.18.8 Conclusions and Future Directions.VOLUME 2.Part V Drug Delivery to the Brain.19 The Blood-Brain Barrier: Roles of the Multidrug Resistance Transporter P-Glycoprotein (Sandra Turcotte, Michel Demeule, Anthony Regina, Chantal Fournier, Julie Jodoin, Albert Moghrabi, and Richard Beliveau).19.1 Introduction.19.2 The Multidrug Transporter P-Glycoprotein.19.3 Localization and Transport Activity of P-gp in the CNS.19.4 Polymorphisms of P-gp.19.5 Role of P-gp at the BBB.19.6 Conclusions.20 Targeting of Neuropharmaceuticals by Chemical Delivery Systems (Nicholas Bodor and Peter Buchwald).20.1 Introduction.20.2 The Blood-Brain Barrier.20.3 Brain-Targeted Drug Delivery.20.4 Chemical Delivery Systems.20.5 Brain-Targeting CDSs.20.6 Molecular Packaging.21 Drug Delivery to the Brain by Internalizing Receptors at the Blood-Brain Barrier (Pieter J. Gaillard, Corine C. Visser, and Albertus (Bert) G. de Boer).21.1 Introduction.21.2 Blood-Brain Barrier Transport Opportunities.21.3 Drug Delivery and Targeting Strategies to the Brain.21.4 Receptor-Mediated Drug Delivery to the Brain.21.5 Transferrin Receptor.21.6 Insulin Receptor.21.7 LRP1 and LRP2 Receptors.21.8 Diphtheria Toxin Receptor.21.9 Conclusions.Part VI Vascular Perfusion.22 Blood-Brain Transfer and Metabolism of Oxygen (Albert Gjedde).22.1 Introduction.22.2 Blood-Brain Transfer of Oxygen.22.3 Oxygen in Brain Tissue.22.4 Flow-Metabolism Coupling of Oxygen.22.5 Limits to Oxygen Supply.22.6 Experimental Results.23 Functional Brain Imaging (Gerald A. Dienel).23.1 Molecular Imaging of Biological Processes in Living Brain.23.2 Overview of Brain Imaging Methodologies.23.3 Imaging Biological Processes in Living Brain: Watching and Measuring Brain Work.23.4 Molecular Probes are Used for a Broad Spectrum of Imaging Assays in Living Brain.23.5 Optical Imaging of Functional Activity by Means of Extrinsic and Intrinsic Fluorescent Compounds.23.6 Tracking Dynamic Movement of Cellular Processes and Cell Types.23.7 Evaluation of Exogenous Genes, Cells, and Therapeutic Efficacy.23.8 Summary and Perspectives.Part VII Disease-Related Response.24 Inflammatory Response of the Blood-Brain Interface (Pedro M. Faustmann and Claus G. Haase).24.1 Introduction.24.2 Diagnostic Features of Cerebrospinal Fluid.24.3 Acute Bacterial Meningitis.24.4 Inflammatory Response in Acute Trauma.24.5 Inflammatory Response in Alzheimer's Disease.25 Stroke and the Blood-Brain Interface (Marilyn J. Cipolla).25.1 Introduction.25.2 Brain Edema Formation During Stroke.25.3 Role of Astrocytes in Mediating Edema During Ischemia.25.4 Cellular Regulation of Cerebrovascular Permeability.25.5 Reperfusion Injury.25.6 Transcellular Transport as a Mechanism of BBB Disruption During Ischemia.25.7 Mediators of EC Permeability During Ischemia.25.8 Hyperglycemic Stroke.25.9 Hemodynamic Changes During Ischemia and Reperfusion and its Role in Cerebral Edema.26 Diabetes and the Consequences for the Blood-Brain Barrier (Arshag D. Mooradian).26.1 Introduction.26.2 Histological Changes in the Cerebral Microvessels.26.3 Functional Changes in the Blood-Brain Barrier.26.4 Potential Mechanisms of Changes in the BBB.26.5 Potential Clinical Consequences of Changes in the BBB.26.6 Conclusions.27 Human Parasitic Disease in the Context of the Blood-Brain Barrier - Effects, Interactions, and Transgressions (Mahalia S. Desruisseaux, Louis M. Weiss, Herbert B. Tanowitz, Adam Mott, and Danny A. Milner).27.1 Introduction (by D. Milner).27.2 Malaria: The Plasmodium berghei Mouse Model and the Severe Falciparum Malaria in Man (by M.S. Desruisseaux and D. Milner).27.3 Trypanosomiasis: African and American Parasites of Two Distinct Flavors (by H. Tanowitz, M.S. Desruisseaux,and A. Mott).27.4 Toxoplasmosis: Transgression, Quiescence, and Destructive Infections (by L. Weiss).27.5 Conclusion.28 The Blood Retinal Interface: Similarities and Contrasts with the Blood-Brain Interface (Tailoi Chan-Ling).28.1 Introduction.28.2 The Inner and Outer BRB.28.3 The Choroidal Vasculature.28.4 Characteristics of Intraretinal Blood Vessels.28.5 Ensheathment and Induction of the Inner BRB by Astrocytes and Muller Glia.28.6 BRB Properties of Newly Formed Vessels.28.7 Pericytes and the BRB.28.8 Membrane Proteins of Tight Junctions.28.9 Localization of Occludin and Claudin-1 to Tight Junctions of Retinal Vascular Endothelial Cells.28.10 Expression of Occludin by RPE Cells and Lack of Occludin Expression by Choroidal Vessels.28.11 Inherent Weakness of the BRB and Existence of Resident MHC Class II+ Cells Predisposes the Optic Nerve Head to Inflammatory Attack.28.12 Clinical and Experimental Determination of the Blood-Retinal Barrier.28.13 Conclusions.Subject Index.