Pharmacology of the Blood Brain. Barrien Targeting CNS Disorders

Transcription

1 >VOLUME SEVENTY ONE ADVANCES IN PHARMACOLOGY Pharmacology of the Blood Brain Barrien Targeting CNS Disorders Edited by THOMAS P. DAVIS Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA Serial Editor S. J. ENNA Department of Molecular and Integrative Physiology, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA Managing Editor LYNN LECOUNT University of Kansas Medical Center SchooI of Medicine, Kansas City, Kansas, USA AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK OXFORD PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO Academic Press is an imprint of Elsevier

2 CONTENTS Preface Contributors xi xiii 1. ABC Transporter Regulation by Signaling at the Blood-Brain Barrien Relevance to Pharmacology 1 David S. Miller 1. Introduction 2 2. ABC Transporters at the Blood-Brain Barrier 4 3. ABC Transporter Regulation 7 4. Conclusion 20 Conflict of Interest 20 Acknowledgments 20 References P-glycoprotein Trafficking as a Therapeutic Target to Optimize CNS Drug Delivery 25 Thomas P. Davis, Lucy Sanchez-Covarubias, and Margaret E. Tome 1. Introduction The BBB/Neurovascular Unit Endothelial Cells and the BBB Transport Across the Brain ßarriers P-glycoprotein Drug Delivery to the CNS: Strategies Developed to Circumvent Brain Barrier Sites Inhibition of Brain Barrier Efflux Transporters Conclusion 39 Conflict of Interest 41 Acknowledgments 41 References Functional Expression of Drug Transporters in Glial Cells: Potential Role on Drug Delivery to the CNS 45 Tamima Ashraf, Amy Kao, and Reina Bendayan 1. Introduction Physiological Role of the BBB and Brain Parenchymal Cellular Compartments 47

3 vi Contents 3. Functional Expression of Drug Transporters in Glial Cells Regulation of Drug Transporters in Glial Cells in the Context of Neuropathologies Conclusion 93 Conflicts of Interest 94 Acknowledgments 94 References Blood-Brain Barrier Na Transporters in Ischemic Stroke 113 Martha E. O'Donnell 1. Introduction Ion Transporters and Channels of the BBB BBB Na-K-Cl Cotransport and Na/H Exchange in Ischemic Stroke and Cerebral Edema Signaling Mechanisms: Roles of AMP Kinase and p38, JNK and ERK MAP Kinases Hormonal and Metabolie Factor Effects on BBB Na Transporter Expression and Activities Future Directions Conclusion 136 Conflicts of Interest 136 Acknowledgments 136 References Transcytosis of Macromolecules at the Blood-Brain Barrier 147 Jane E. Preston, N. Joan Abbott, and David J. Begley 1. Introduction Mechanisms of Macromolecule Transcytosis Endocytosis in Brain Endothelia Vesicle Trafficking and Subcellular Localization in Brain Endothelia Recycling ofvesicles to Apical or Basolateral Membranes Exocytosis in Endothelia Targeting Receptor-Mediated Transport for Drug Delivery to Brain Conclusion 159 Conflict of Interest 160 References Drug Delivery to the Ischemic Brain 165 Brandon J. Thompson and Patrick T. Ronaldson 1. Introduction ^6 2. Pathophysiology of Ischemia 167

4 Contents vii 3. Drug Delivery to the Hypoxic/Ischemic Brain Conclusion 191 Conflict of Interest 192 References Delivery of Chemotherapeutics Across the Blood-Brain Barrier: Challenges and Advances 203 Nancy D. Doolittle, Leslie L. Muldoon, Aliana Y. Culp, and Edward A. Neuwelt 1. Introduction Blood-Brain Barrier Disruption Primary CNS Lymphoma Chemoprotection Studies Advances in Neuroimaging Conclusion 235 Conflict of Interest 236 Acknowledgments 237 References Delivery of Antihuman African Trypanosomiasis Drugs Across the Blood-Brain and Blood-CSF Barriers 245 Gayathri N. Sekhar, Christopher P. Watson, Mehmet Fidanboylu, Lisa Sanderson, and Sarah A. Thomas 1. Introduction A Brief History of HAT Clinical Presentation of the Disease Unique Diagnostic Markers Vector Diagnosis of HAT Treatment of HAT Parasite Resistance: Is Combination Therapy the Way Forward? BBB Transport of Anti-HAT Drugs Latest Research Developments Conclusion 268 Conflict of Interest 268 Acknowledgments 268 References Delivery of Therapeutic Peptides and Proteins to the CNS 277 Therese S. Salameh and William A. Banks 1. Introduction 2. Obstacles to Delivering Protein and Peptides to the CNS

5 viii Contents 3. Saturable Mechanisms of Peptide and Protein Passage Across the BBB Strategies to Enhance the Delivery of Proteins and Peptides to the CNS Conclusion 292 Conflict of Interest 292 Acknowledgments 292 References Engineering and Pharmacology of Biood-Brain Barrier-Permeable Bispecific Antibodies 301 Danica Stanimirovic, Kristin Kemmerich, Arsalan S. Haqqani, and Graham K. Farrington 1. Introduction Making the Case for Antibodies as Central Nervous System Therapeutics BBB Shuttles for Macromolecules Engineering BBB-Permeable Bispecific Antibodies Analytical Challenges and Pharmacokinetics/Pharmacodynamics Models Conclusion 328 Conflict of Interest 328 References Pharmacological Significance of Prostaglandin E 2 and D 2 Transport at the Brain Barriers 337 Masanori Tachikawa, Ken-ichi Hosoya, and Tetsuya Terasaki 1. Introduction Roles and Kinetics of PGE 2 and PGD 2 in the CNS Transporters for PGs and Interspecies Differences PGE 2 Efflux Transport System at the BBB PGE 2 and PGD 2 Efflux Transport Systems at the BCSFB Conclusion 355 Conflict of Interest 356 Acknowledgments 356 References Steroids and the Blood-Brain Barrier: Therapeutic Implications 361 Ken A. Witt and Karin E. Sandoval 1. Introduction Blood-Brain Barrier Steroids and the Brain Steroid:BBB Interaction 370

6 Contents ix 5. Conclusion 381 Conflict of Interest 382 References Combination Approaches to Attenuate Hemorrhagic Transformation After tpa Thrombolytic Therapy in Patients with Poststroke Hyperglycemia/Diabetes Xiang Fan, Yinghua Jiang, Zhanyang Yu, Jing Yuan, Xiaochuan Sun, Shuanglin Xiang, Eng H. Lo, and Xiaoying Wang 1. Introduction 2. Increased Hemorrhagic Transformation After tpa Thrombolytic Therapy 3. Underlying Mechanisms: Multiple Pathological Pathways 4. DM and Hyperglycemia-Mediated Vascular Pathology 5. Ischemic Stroke and BBB Disruption 6. tpa and Extracellular Proteolysis Dysfunction-Mediated BBB Disruption 7. Multiple Pathological Factors and Interactions 8. Combination Approaches in Focal Embolic Stroke Model of Hyperglycemia/Diabetic Rats 9. Conclusion Conflict of Interest References Aging, the Metabolie Syndrome, and Ischemic Stroke: Redefining the Approach for Studying the Blood-Brain Barrier in a Complex Neurological Disease 411 Brandon P. Lucke-Wold, Arie F. Logsdon, Ryan C. Turner, Charles L. Rosen, and Jason D. Huber 1. Introduction Cell Aging Age and the Metabolie Syndrome Linking Metabolie Syndrome and Aging Conclusion 434 Conflict of Interest 435 References Drug Abuse and the Neurovascular Unit 451 Richard D. Egleton and Thomas Abbruscato 1. Introduction Molecular Targets of Common Substances of Abuse 452

7 X Contents 3. The Neurovascular Unit Transport of Drugs of Abuse into the Brain Regulation of the NVU by Drugs of Abuse Conclusion 470 Conflict of Interest 471 References 471 Index 481