Flanagan Providing Pharmacological Access to the Brain

Alternate Approaches
1. Auflage 2013
ISBN: 978-1-4832-8835-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 21, 508 Seiten

Reihe: Methods in Neurosciences

This volume focuses on contemporary approaches for delivering experimental and therapeutic agents into the brain. The contributions provide methodological details that are typically not available in the literature. Subtleties and shortcuts critical to each procedure are included to facilitate their use by both the experienced researcher and novice.Highlights* Polymeric, cellular, and molecular drug delivery* Neuropharmacology* Blood-brain barrier* Central nervous system

Autoren/Hrsg.

Flanagan, Thomas R.

Inhaltsverzeichnis

1;Front Cover
;1
2;Providing Pharmacological Access to the Brain: Alternate Approaches
;4
3;Copyright Page
;5
4;Table of Contents;6
5;Contributors to Volume 21;10
6;Preface;16
7;Methods in Neurosciences;18
8;Section I: Characterizing the Blood-Brain Barrier
;20
8.1;Chapter [1]. Cellular Response of Central Nervous System Tissue to Invasive Therapeutic Measures
;22
8.1.1;Introduction;22
8.1.2;Definition of Cellular Response to Injury;22
8.1.3;Definition of Trophic Mechanisms of Injury Response;27
8.1.4;Models for Therapeutic Manipulation;29
8.1.5;Efficacy of Therapeutic Measures;35
8.1.6;Efficacy of Therapeutic Measures;35
8.1.7;Conclusions;36
8.1.8;References;37
8.2;Chapter [2]. Models of Angiogenesis and the Blood-Brain Barrier
;39
8.2.1;Introduction;39
8.2.2;Techniques for Localization of Proliferating Vasculature (Angiogenesis)
;40
8.2.3;Strategies for Determining Temporal Sequence and Source of Neovascularization in Neural Transplants
;44
8.2.4;Techniques to Determine Blood-Brain Barrier Permeability;46
8.2.5;Acknowledgments;50
8.2.6;References;50
9;Section II: Transiently Removing the Blood-Brain Barrier
;52
9.1;Chapter [3]. Osmotic Opening of the Blood-Brain Barrier and Brain Tumor Chemotherapy
;54
9.1.1;Introduction;54
9.1.2;Osmotic Opening of Blood-Brain Barrier;58
9.1.3;Size Dependence of Blood-Brain Barrier Permeability;59
9.1.4;Osmotic Opening and Brain Tumor Chemotherapy;62
9.1.5;Conclusions;66
9.1.6;References;67
9.2;Chapter [4]. Osmotic Blood-Brain Barrier Modification: Increasing Delivery of Diagnostic and Therapeutic Agents to the Brain
;71
9.2.1;Introduction;71
9.2.2;Blood-Brain Barrier;71
9.2.3;Blood-Brain Barrier Disruption;72
9.2.4;Development of Animal Models;73
9.2.5;Confirming Blood-Brain Barrier Disruption;78
9.2.6;Factors Influencing Successful Blood-Brain Barrier Disruption and Agent Delivery
;78
9.2.7;Conclusion;84
9.2.8;References;84
10;Section III: Facilitated Transport through the Blood-Brain Barrier
;88
10.1;Chapter [5]. Peripheral Administration of Nerve Growth Factor Conjugated to an Anti-transferrin Receptor Antibody Increases Cholinergic Neuron Survival in Intraocular Forebrain Transplants
;90
10.1.1;Introduction;90
10.1.2;Methods and Results;93
10.1.3;Concluding Remarks;108
10.1.4;Acknowledgments;109
10.1.5;References;109
10.2;Chapter [6]. Ferrotransferrin and Antibody against the Transferrin Receptor as Potential Vehicles for Drug Delivery across the Mammalian Blood-Brain Barrier into the Central Nervous System
;112
10.2.1;Introduction;112
10.2.2;Iron, Transferrin, and Transferrin Receptor;114
10.2.3;Preparation and Application of Ferrotransferrin and Antibody against the Ferrotransferrin Receptor
;115
10.2.4;Analyses of Potential Transcytosis of Blood-Borne, Receptor-Mediated Probe Molecules across the Blood-Brain Barrier
;122
10.2.5;Transendothelial Pathways for Ferrotransferrin and Antibody against the Ferrotransferrin Receptor as Vehicles for Circumventing the Blood-Brain Barrier
;128
10.2.6;Summary and Conclusions;134
10.2.7;Acknowledgments;135
10.2.8;References;135
10.3;Chapter [7]. DepoFoam-Mediated Drug Delivery into Cerebrospinal Fluid
;137
10.3.1;Introduction;137
10.3.2;Synthesis of DepoFoam-Encapsulated Ara-C (DTC 101);138
10.3.3;Preparation of DepoFoam-Encapsulated Methotrexate (Depo/MTX);138
10.3.4;Preparation of Depo/Morphine;138
10.3.5;Synthesis of Depo/IFN;139
10.3.6;Central Nervous System Pharmacokinetic Analysis;140
10.3.7;Intraventricular Pharmacokinetics of DTC 101 in Rats;141
10.3.8;Intralumbar Pharmacokinetics of DTC 101 in Monkeys;142
10.3.9;Intracisternal Pharmacokinetics with Depo/MTX in Rats;143
10.3.10;Intraventricular Pharmacokinetics of DTC 101 in Humans;147
10.3.11;Summary;149
10.3.12;Acknowledgments;150
10.3.13;References;150
11;Section IV: Polymeric Release Systems for the Central Nervous System
;152
11.1;Chapter [8]. Interstitial Drug Delivery to the Central Nervous System Using Controlled Release Polymers: Chemotherapy for Brain Tumors
;154
11.1.1;Introduction;154
11.1.2;Methods;155
11.1.3;Results;163
11.1.4;Conclusions;167
11.1.5;References;167
11.2;Chapter [9]. Sustained Intracerebral Delivery of Nerve Growth Factor with Biodegradable Polymer Microspheres
;169
11.2.1;Introduction;169
11.2.2;Methods;173
11.2.3;Results;178
11.2.4;Summary;184
11.2.5;Acknowledgments;185
11.2.6;References;185
11.3;Chapter [10]. Polymerie Drug Carrier Systems in the Brain
;188
11.3.1;Introduction;188
11.3.2;Polymers for Drug Delivery;189
11.3.3;Nondegradable Implants for Treatment of Brain Cancer;190
11.3.4;Biodegradable Implants for Treatment of Brain Cancer;191
11.3.5;Delivery of Neurotransmitters and Neuromodulators;197
11.3.6;Concluding Remarks;199
11.3.7;References;200
12;Section V: Using Pump Delivery Devices within the Brain
;204
12.1;Chapter [11]. Using Osmotic Minipumps for Intracranial Delivery of Amino Acids and Peptides
;206
12.1.1;Intracerebroventricular Injection versus Microinjection into Brain;207
12.1.2;Minipump Delivery Systems;210
12.1.3;Practical Considerations for Cannulation and Minipump Use;212
12.1.4;Summary;218
12.1.5;Acknowledgments;218
12.1.6;References;218
12.2;Chapter [12]. Continuous Central Nervous System Infusion with Alzet Osmotic Pumps
;220
12.2.1;Introduction;220
12.2.2;Construction of Infusion Devices;221
12.2.3;Preimplantation Preparation of Pumps and Infusion Devices;225
12.2.4;Infusion/Treatment Protocols;227
12.2.5;Stereotaxic Surgery;228
12.2.6;Experimental Examples;230
12.2.7;Conclusion;231
12.2.8;Acknowledgments;231
12.2.9;References;232
12.3;Chapter [13]. Injection of Biologically Active Substances into the Brain
;233
12.3.1;Introduction;233
12.3.2;Getting Started;235
12.3.3;Preparing Guide Cannula and Stylet;236
12.3.4;Inserting Guide Cannula-Stylet Assembly;240
12.3.5;Injecting Solutions;241
12.3.6;Injecting Solutions into Ventricular System;245
12.3.7;Unilateral 6-Hydroxydopamine Lesions;246
12.3.8;Injection of Cells into Brain Parenchyma;248
12.3.9;Acknowledgments;253
12.3.10;References;253
13;Section VI: Using Implanted Living Tissues within the Brain
;254
13.1;Chapter [14]. Factors Important in the Survival of Dopamine Neurons in Intracerebral Grafts of Embryonic Substantia Nigra
;256
13.1.1;Introduction;256
13.1.2;Nigral Grafts;257
13.1.3;Use of Cell Suspensions and Vital Stains;264
13.1.4;Use of in Vitro Cultures;265
13.1.5;In Vivo Intracerebral Grafts;267
13.1.6;Conclusions;268
13.1.7;Acknowledgments;269
13.1.8;References;269
13.2;Chapter [15] Techniques in Adrenal Medullary Transplantation for Experimental Nonhuman Primate Parkinsonism
;272
13.2.1;Adrenalectomy in Nonhuman Primate;273
13.2.2;Peripheral Nerve Harvesting in Nonhuman Primate;280
13.2.3;Striatal Grafting and Cografting for Nonhuman Primate Parkinsonian Syndromes
;282
13.2.4;Concluding Remarks;289
13.2.5;Acknowledgments;290
13.2.6;References;290
13.3;Chapter [16]. Technical Aspects of Transplantation of the Adrenal Medulla to the Caudate Nucleus as a Treatment for Parkinson's Disease
;291
13.3.1;Introduction;291
13.3.2;Overview of Procedure;291
13.3.3;Preparation of Adrenal Medulla;293
13.3.4;Conclusions;295
13.3.5;References;295
14;Section VII: Creating Cell Lines for Transplant Therapies
;298
14.1;Chapter [17]. Transplantation of Epidermal Growth Factor-Responsive Neural Stem Cell Progeny into the Murine Central Nervous System
;300
14.1.1;Introduction;300
14.1.2;Production and in Vitro Characterization of Epidermal Growth Factor-Responsive Neural Stem Cells
;302
14.1.3;Identification of Stem Cell Progeny and Their Differentiation Potential in Vitro
;302
14.1.4;Formation of Myelinating Oligodendrocytes by Epidermal Growth Factor-Responsive Stem Cell Progeny when Transplanted in Vivo
;304
14.1.5;Differentiation and Survival of Epidermal Growth Factor-Responsive Stem Cells, Genetically Tagged with Escherichia coli ß-Galactosidase Gene, When Implanted into Mouse Cerebral Cortex
;308
14.1.6;Transgenic Mouse-Derived Neural Stem Cells: A Source of Marked Glial Cells for Central Nervous System Transplantation
;309
14.1.7;Conclusions;311
14.1.8;Acknowledgments;311
14.1.9;References;311
14.2;Chapter [18]: Application of Astrocyte Transplants as a Therapeutic Intervention
;313
14.2.1;Introduction;313
14.2.2;Methodological Considerations for Implantation;313
14.2.3;Preparation and Implantation of Astrocytes into Brain;315
14.2.4;Characterization of Astrocyte Implants;319
14.2.5;Summary;323
14.2.6;References;325
14.3;Chapter [19]. Development of Immortalized Cell Lines for Transplantation in Central Nervous System Injury and Degeneration Models
;327
14.3.1;Introduction;327
14.3.2;General Guidelines;328
14.3.3;Establishment of Immortalized Cell Line;329
14.3.4;Selection and Characterization;332
14.3.5;Differentiation;334
14.3.6;Cell Labeling;335
14.3.7;Transplantation;337
14.3.8;Conclusions;340
14.3.9;References;342
15;Section VIII: Using Implanted Living Cells within the Central Nervous System
;346
15.1;Chapter [20]. Use of Genetically Modified Cells to Deliver Neurotrophic Factors and Neurotransmitters to the Brain
;348
15.1.1;Introduction;348
15.1.2;In Vitro Development and Characterization of Engineered Cells;350
15.1.3;In Vivo Characterizations of Engineered Cells;354
15.1.4;Summary;365
15.1.5;Acknowledgments;365
15.1.6;References;365
15.2;Chapter [21]. Neuropeptide and Catecholamine Delivery to Central Nervous System by Implanted Chromaffin Cells
;367
15.2.1;Introduction;367
15.2.2;Graft Preparations;368
15.2.3;Spinal Subarachnoid Grafts;369
15.2.4;Intraparenchymal Grafts;377
15.2.5;Conclusions;386
15.2.6;Acknowledgment;386
15.2.7;References;386
16;Section IX: Using Implanted Encapsulated Cells within the Brain
;388
16.1;Chapter [22]. Microencapsulation of Cells in Thermoplastic Copolymer (Hydroxyethyl Methacrylate-Methyl Methacrylate)
;390
16.1.1;Introduction;390
16.1.2;Materials and Methods;391
16.1.3;Illustrative Results;398
16.1.4;Conclusions;404
16.1.5;Acknowledgments;404
16.1.6;References;404
16.2;Chapter [23]. Hydrogel Applications for Encapsulated Cellular Transplants
;406
16.2.1;Introduction;406
16.2.2;Cellular Preparations;407
16.2.3;Matrix Preparations;408
16.2.4;Microencapsulation Process;409
16.2.5;Macroencapsulation;414
16.2.6;Assessment;415
16.2.7;Concluding Remarks;421
16.2.8;Acknowledgments;422
16.2.9;References;422
16.3;Chapter [24]. Tests for Validating the Safety of Encapsulated Xenografts
;424
16.3.1;Introduction;424
16.3.2;Xenogeneic Cells in Transplants;424
16.3.3;Tests for Uniformity of Immunoisolation Devices;425
16.3.4;Qualitative Issues;432
16.3.5;Quantitative Issues;435
16.3.6;Testing, Implanting, and Removing Devices;437
16.3.7;Conclusion;442
16.3.8;References;442
17;Section X: Induced Gene Expression in Intrinsic Central Nervous System Cells with DNA Injected into the Brain
;446
17.1;Chapter [25]. Particle Bombardment for Gene Transfer into Nerve Cell Systems
;448
17.1.1;Introduction;448
17.1.2;Accell Gene Transfer Technique;449
17.1.3;Application to Central Nervous System Primary Cultures and Cell Expiants
;452
17.1.4;Application to Mammalian Somatic Tissues in General;460
17.1.5;Summary;461
17.1.6;Acknowledgment;462
17.1.7;References;462
18;Section XI: Viral Transfection of Intrinsic Cells within the Brain
;464
18.1;Chapter [26]. A Defective Herpes Simplex Virus Vector System for Genetic Intervention in the Adult Brain: Applications to Gene Therapy and Neuronal Physiology
;466
18.1.1;Introduction: Genetic Intervention in Brain;466
18.1.2;Strategies for Manipulation of Neuronal Physiology by Genetic Intervention
;468
18.1.3;Gene Therapy Approaches with HSV-1 Vectors;471
18.1.4;Defective HSV-1 Vector System for Gene Transfer into Neuronal Cells
;473
18.1.5;Alteration of Neuronal Physiology by Expression of Unregulated Adenylate Cyclase in Neurons
;480
18.1.6;Summary;482
18.1.7;References;483
18.2;Chapter [27]. Expression of Neurotrophic Genes from Herpes Simplex Virus Type 1 Vectors: Modifying Neuronal Phenotype
;485
18.2.1;Introduction;485
18.2.2;Amplicon Vector System;486
18.2.3;Packaging of Defective HSV-1 Viral Vectors;487
18.2.4;Specifics about Packaging Procedure;488
18.2.5;Analysis of Viral Stocks;491
18.2.6;Troubleshooting;495
18.2.7;Viral Transduction;496
18.2.8;Other Viral Vectors Systems;500
18.2.9;Safety and Other Issues Related to Vector Use;502
18.2.10;Summary;503
18.2.11;Acknowledgments;503
18.2.12;References;503
19;Section XII: Predicting the Future of Central Nervous System Delivery System Technologies
;506
19.1;Chapter [28]. Assessing Commercial Potential of Central Nervous System Delivery Approaches
;508
19.1.1;Introduction;508
19.1.2;Assessing Market Size and Value;508
19.1.3;Identifying Key Issues for Analysis;510
19.1.4;Identifying Competitive Therapeutic, Economic, and Societal Advantages
;514
19.1.5;Ranking Therapeutic Approaches;514
19.1.6;Predicting Breakthroughs;518
19.1.7;Additional Assessments;520
19.1.8;Conclusion;521
19.1.9;References;521
20;Index;522
21;Color Plate
;412

Leseproben

Contributors to Volume 21

J. Babensee,     (22), Departments of Chemical Engineering and Applied Chemistry, Center for Biomaterials, University of Toronto, Toronto, Ontario, Canada M5S 1A4

Cristina Bäckman,     (5), Department of Basic Science, University of Colorado Health Sciences Center, Denver, Colorado 80262

Belinda J. Baker,     (6), Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892

William Banks

(6), Section of Medicine, Veterans Affairs Medical Center, New Orleans, Lousiana 70146

Department of Medicine, Tulane University, School of Medicine, New Orleans, Louisiana 70118

Roger Barker,     (14), MRC Cambridge Centre for Brain Repair, and Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Martin Berry,     (1), Department of Anatomy and Cell Biology, United Medical and Dental Schools, London SE1 9RT, United Kingdom

Paul T. Biddle,     (5), Department of Basic Science, University of Colorado Health Sciences Center, Denver, Colorado 80262

Henry Brem,     (8), Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Richard J. Bridges,     (18), Department of Pharmaceutical Science, School of Pharmacy, University of Montana, Missoula, Montana 59812

Richard D. Broadwell,     (6), Office of Research Integrity, U.S. Public Health Service, Rockville, Maryland 20852

Paul J. Camarata,     (9), Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota 55455

Stephen W. Carmichael,     (16), Department of Anatomy, Mayo Clinic/ Mayo Foundation, Rochester, Minnesota 55905

Paul M. Carvey,     (13), Department of Neurological Sciences, Neuropharmacology Research Laboratories, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612

Gordon R. Chalmers,     (20), Department of Neurosciences, University of California, San Diego, La Jolla, California 92093

U. De Boni,     (22), Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A4

E. Doherty,     (24), CytoTherapeutics, Inc., Providence, Rhode Island 02906

Abraham J. Domb,     (10), Department of Pharmaceutical Chemistry and the Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel 91120

Ian D. Duncan,     (17), School of Veterinary Medicine, University of Wisconsin–Madison, Madison, Wisconsin 53706

Stephen B. Dunnett,     (14), MRC Cambridge Centre for Brain Repair, and Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Mathew J. During,     (26), Neuroendocrine Program, Yale University School of Medicine, New Haven, Connecticut 06510

Ted Ebendal,     (5), Department of Developmental Biology, Uppsala University, S–751 23 Uppsala, Sweden

Timothy J. Ebner,     (9), Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota 55455

D.F. Emerich,     (24), CytoTherapeutics, Inc., Providence, Rhode Island 02906

Howard Federoff,     (27), Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461

Massimo S. Fiandaca,     (15), Department of Neurosurgery, The Johns Hopkins Medical Center, Baltimore, Maryland 21287

Lisa J. Fisher,     (20), Department of Neurosciences, University of California, San Diego, La Jolla, California 92093

Thomas R. Flanagan,     (24, 28), Chatham Associates, Barrington, Rhode Island 02806

W.J. Freed,     (19), National Institute of Mental Health, National Institute of Health, Neuroscience Center at St. Elizabeths, Washington, D. C. 20032

Rosemary Fricker,     (14), MRC Cambridge Centre for Brain Repair, and Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Phillip Friden,     (5, 6), Alkermes, Inc., Cambridge, Massachusetts 02139

B. Frydel,     (24), CytoTherapeutics, Inc., Providence, Rhode Island 02906

Fred H. Gage,     (20), Department of Neurosciences, University of California, San Diego, La Jolla, California 92093

Alfred I. Geller,     (26), Division of Endocrinology, Children’s Hospital, Boston, Massachusetts 02115

H.M. Geller,     (19), Department of Pharmacology, University of Medicine and Dentistry at New Jersey, Robert Wool Johnson Medical School, Piscataway, New Jersey 08854

Greg Gerhardt,     (5), Departments of Pharmacology and Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado 80262

Michael D. Geschwind,     (27), Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461

M. Giordano,     (19), National Institute of Mental Health, National Institute of Health, Neuroscience Center at St. Elizabeths, Washington, D. C. 20032

Ann-Charlotte Granholm,     (5), Department of Basic Science, University of Colorado Health Sciences Center, Denver, Colorado 80262

Theo Hagg,     (12), Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Joseph P. Hammang,     (17), Cell and Molecular Neurobiology, CytoTherapeutics, Inc., Providence, Rhode Island 02906

Barry Hoffer,     (5), Departments of Pharmacology and Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado 80262

V. Horvath,     (22), Departments of Chemical Engineering and Applied Chemistry, Center for Biomaterials, University of Toronto, Toronto, Ontario, Canada M5S 1A4

Shoushu Jiao,     (25), Department of Pediatrics and Medical Genetics, Waisman Center, University of Wisconsin–Madison, Wisconsin 53705

Patrick J. Kelly,     (16), Department of Neurologic Surgery, Mayo Clinic/ Mayo Foundation, Rochester, Minnesota 55905

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