Implications of the Blood-Brain Barrier and Its Manipulation

Volume 2 Clinical Aspects
Herausgegeben von Neuwelt, E.A.

• Broschiertes Buch

Produktbeschreibung

As a neurologist and student of the microvasculature, I find great pleasure in introducing this treatise. Presented here is a view of brain pathophysiology and therapy from the perspective of the blood-brain barrier (BBB). Virtually every disease process that affects the brain-traumatic, neoplastic, infectious, inflammatory, toxic, metabolic, degenera tive, vascular, and epileptic-affects the BBB. Damage to this homeostatic system often leads to disruption of the composition and volume of brain fluid compartments, thereby contributing to neurologic symptoms and pathology. Furthermore, in disorders in which the integrity of the barrier is not breached, its normal restrictive nature may limit therapeu tic approaches. For example, the barrier appears to function normally in Parkinson dis ease, but its ability to compensate for striatal dopamine depletion is in part determined by the activity of transporters and enzymes operative in the brain microvasculature. of antibiotics, anticonvulsants, antineoplastic agents, and neurolep Similarly, the choice tics requires attention to these drugs' interaction with the BBB. Thus, the barrier inter faces with virtually all nervous system diseases and therapies. Future brain treatments with regulatory peptides, immune mediators, and gene components will require selective methods to deliver these agents to specific brain regions. The second volume of this text successfully provides a thorough review of BBB function and failure in a variety of clinical situations.

Produktdetails

• Verlag: Springer / Springer US / Springer, Berlin
• Artikelnr. des Verlages: 978-1-4615-7257-2
• Softcover reprint of the original 1st ed. 1989
• Seitenzahl: 668
• Erscheinungstermin: 10. August 2012
• Englisch
• Abmessung: 254mm x 178mm x 36mm
• Gewicht: 1236g
• ISBN-13: 9781461572572
• ISBN-10: 1461572576
• Artikelnr.: 37479463

Inhaltsangabe

14. CNS Imaging and the Brain Barriers.- 1. Introduction.- 2. The Blood-Brain Barrier and Selective Permeability.- 3. Contrast Media and Computed Tomography.- 3.1. Blood-Brain Barrier and Contrast Enhancement in Computed Tomography.- 3.2. Pathologic Alterations in the BBB and Their Relevance to CT Enhancement.- 4. Injections of Water-Soluble Contrast Media in Neuroradiology.- 4.1. Intracarotid Injections of Water-Soluble Contrast Media.- 4.2. Intrathecal Contrast Media.- 5. Single Photon Emission Computed Tomography.- 5.1. Nondiffusible Radionuclides.- 5.2. Diffusible Radionuclides.- 6. Positron Emission Tomography.- 7. Magnetic Resonance Imaging and the Brain Barriers.- 8. Conclusion.- References.- 15. Effect of Steroids on the Blood-Brain Barrier.- 1. History.- 2. Clinical Effects of Steroids on the Various Diseases That Disrupt the Blood-Brain Barrier.- 2.1. Tumor-Induced Brain Edema.- 2.2. Brain Abscess.- 2.3. Head Injury.- 2.4. Cerebral Ischemia.- 3. Effects of Steroids on Peritumoral Edema.- 3.1. Effects of Steroids on Brain Water and Electrolyte Content.- 3.2. Capillary Permeability of the Tumor-Bearing Brain and Effects of Steroids on Modification of Permeability.- 3.3. Cerebral Blood Flow in Peritumoral Brain Tissue and the Effects of Steroid Treatment.- 3.4. Cerebral Glucose Metabolism and Effect of Steroids.- 3.5. Protein Synthesis in Edematous Brain Tissue.- 3.6. Distribution of Steroids in Peritumoral Brain Tissue.- 4. Summary and Conclusions.- References.- 16. Brain Tumors and the Blood-Tumor Barrier.- 1. Introduction.- 1.1. Primary Brain Tumors.- 1.2. Metastatic Brain Tumors.- 2. Vasculature of CNS Tumors.- 2.1. Historic Perspective.- 2.2. Morphology of Tumor Blood Vessels.- 2.3. Structural Basis of Increased Tumor Permeability.- 3. Angiogenesis and the Determination of Capillary Type.- 4. Quantitative Studies of Permeability and Blood Flow within CNS Tumors.- 5. Pharmacologic Considerations and Conclusions.- References.- 17A. Blood-Brain Barrier Disruption in the Treatment of Brain Tumors: Animal Studies.- 1. Introduction.- 1.1. Basic Concept of the Blood-Brain Barrier in Tumors.- 1.2. Regulation of Drug Entry into the Central Nervous System.- 1.3. Osmotic Disruption of the Blood-Brain Barrier.- 1.4. Animal Models of Osmotic Blood-Brain Barrier Disruption.- 1.5. Reversibility of Osmotic Disruption.- 1.6. Pathologic and Behavioral Sequelae after Blood-Brain Barrier Disruption.- 2. Animal Studies of Osmotic Blood-Brain Barrier Disruption.- 2.1. Factors Affecting Blood-Brain Barrier Disruption and Drug Delivery.- 2.2. Drug Delivery after Blood-Brain Barrier Disruption.- 2.3. Drug Clearance from Brain after Blood-Brain Barrier Disruption.- 2.4. Monitoring Blood-Brain Barrier Disruption.- 2.5. Neurotoxicity of Chemotherapeutic Agents.- 2.6. Animal Models of Intracerebral Tumor Xenografts.- 2.7. Monoclonal Antibody Delivery to the Central Nervous System after Blood-Brain Barrier Disruption.- 2.8. Monoclonal Antibody Delivery to Intracerebral Tumors.- 2.9. Summary and Future Directions in Experimental Brain Tumor Therapy.- References.- 17B. Blood-Brain Barrier Disruption in the Treatment of Brain Tumors: Clinical Implications.- 1. Introduction.- 2. Clinical Trials of Osmotic BBB Modification in Patients with Malignant Brain Tumors.- 2.1. Technique of Osmotic BBB Modification.- 2.2. Monitoring of Methotrexate Delivery after Osmotic BBB Modification.- 2.3. Documentation of Osmotic BBB Modification by Enhanced CT Scanning.- 2.4. Documentation of Osmotic BBB Modification by Radionuclide Brain Scanning.- 3. Phase II (Efficacy) Studies of Chemotherapy Administered in Conjunction with Osmotic BBB Modification: Current Protocol and Regimen.- 3.1. Results in Patients with Glioblastoma.- 3.2. Results in Patients with Brain Metastases.- 3.3. Results in Patients with Primary CNS Lymphoma.- 3.4. Neurologic and Nonneurologic Complications Associated with Combination Chemotherapy and Osmotic BBB Modification.- 3.5. Maculopathy Associated with Combination Chemotherapy and Osmotic BBB Modification.- 4. Implications for Infusion of Tumor-Specific MAbs in Conjunction with Osmotic BBB Modification.- 4.1. Permeability of Human Brain Tumor to [99mTc]-GH and Albumin.- 4.2. Results of Radiolabeled MAb Delivery to Patients with Melanoma Metastatic to the Brain.- 5. Summary and Conclusions.- References.- 18. Bacterial and Fungal Brain Abscess and the Blood-Brain Barrier.- 1. Introduction.- 2. Clinical Studies.- 3. Experimental Brain Abscess Production.- 4. Imaging of Brain Abscess.- 4.1. Correlation of CT and Neuropathologic Findings.- 4.2. Ultrasound and Brain Abscess.- 4.3. Magnetic Resonance Imaging.- 4.4. Imaging of an Immunocompromised Host.- 5. The BBB and Antibiotic Delivery to Brain and Brain Abscess.- 6. Methods to Disrupt the Blood-Brain Barrier.- 7. Pharmacologic Animal Studies.- 8. Natural History of Brain Abscess in the Rodent.- 9. Differential Permeability of Brain Abscess to Antibiotics versus Antibody.- 10. Fungal Brain Abscess.- 11. Conclusion.- References.- 19. Genetic Enzyme Deficiencies and the Blood-Brain Barrier.- 1. Introduction.- 2. The Significance of Developing an Effective Therapy for Genetic Enzyme Deficiencies.- 3. The Rationale for Various Treatment Strategies.- 4. Problems Associated with Enzyme-Replacement Therapy.- 4.1. Delivery of Enzyme.- 4.2. Production of Enzyme.- 4.3. Protectionof Enzyme.- 4.4. Evaluation of Proposed Therapeutic Strategies.- 5. Past Experiences and Future Possibilities.- 5.1. Direct Replacement of Purified Exogenous Enzyme.- 5.2. Tissue Transplantation as a Means of Enzyme-Replacement Therapy.- 5.3. Replacement of the Gene Coding for the Defective Enzyme.- 6. Conclusion.- References.- 20. The Blood-Brain Barrier and Movement Disorders.- 1. Introduction.- 2. Parkinsonism and Dopaminergic Neurotransmission.- 2.1. Evidence That Parkinsonism Is a Dopamine Deficiency Disorder.- 2.2. Therapeutic Problems.- 2.3. Precursor Therapy.- 2.4. Lipophilic Dopaminergic Agents.- 2.5. Alternative Routes of Administration.- 2.6. Transplantation.- 3. Myoclonus and Serotonergic Neurotransmission.- 3.1. Myoclonus as a Serotonin Deficiency Disorder.- 3.2. Tryptophan and 5-Hydroxytryptophan as Serotonin Precursors.- 3.3. Therapeutic Results.- 4. Chorea, Memory Deficits, and Cholinergic Neurotransmission.- 4.1. Choreic Syndromes and Memory as Acetylcholine Deficiency Disorders.- 4.2. Choline and Lecithin as Acetylcholine Precursors.- 4.3. Diaminoethanol as an Acetylcholine Precursor.- 4.4. Therapeutic Results.- 5. Conclusion.- References.- 21. Chemoradiotherapy Interactions and the Blood-Brain Barrier.- 1. The Clinical Problem.- 1.1. Epidemiology of CNS Tumors and Brain Metastases.- 1.2. Limitations of Cerebrospinal Fluid Chemotherapy.- 1.3. Attempts to Combine Radiotherapy and Chemotherapy.- 1.4. Previous Reviews in Literature.- 2. Laboratory Studies.- 2.1. Radiation Factors.- 2.2. Methotrexate.- 2.3. Cytosine Arabinoside.- 2.4. Other Drugs.- 2.5. Summary.- 3. Clinical Studies.- 3.1. Lack of Evidence for Therapeutic Synergism of Chemoradiotherapy.- 3.2. Methotrexate.- 3.3. Cytosine Arabinoside.- 3.4. Other Drugs.- 3.5. Temporal Factors.- 3.6. Summary.- 4. Future Perspectives.- 4.1. Measures to Increase Therapeutic Efficacy.- 4.2. Measures to Decrease Neurotoxicity.- References.- 22. Hypertension and the Blood-Brain Barrier.- 1. Introduction.- 2. Acute Hypertension.- 2.1. Experimental Models.- 2.2. Why Does It Leak?.- 2.3. Modifying Factors.- 2.4. Neurogenic Influences.- 3. Chronic Hypertension.- 3.1. Renal Hypertension.- 3.2. Genetic Hypertension.- 4. Consequences and Clinical Implications.- 4.1. Potential Risk Situations for Hypertensive Opening of the BBB.- 4.2. Possible Acute and Chronic Effects of Transient BBB Opening.- 4.3. Hypertension and Brain Edema.- 4.4. Acute Hypertensive Encephalopathy.- 4.5. Degenerative Vascular Lesions in Chronic Hypertension.- 4.6. Cerebral Lacunes.- 4.7. Binswanger Encephalopathy.- 5. Summary and Conclusions.- References.- 23. Meningitis, Antimicrobial Agents, and the Blood-Brain Barrier.- 1. Introduction.- 2. Role of the Blood-Brain Barrier in Pathogenesis.- 2.1. Routes of Invasion.- 2.2. Protection of Meninges by the Blood-Brain Barrier.- 2.3. Age-Related Susceptibility.- 2.4. Possible Mechanisms of Invasion.- 3. Effect of Meningitis on the Blood-Brain Barrier.- 3.1. Increased Permeability.- 3.2. Pathologic Findings.- 3.3. CSF Leukocytosis.- 3.4. Containment of Infection.- 3.5. Hypoglycorrhachia.- 4. Importance of Achieving Cidal Concentrations of Antimicrobial Agents in CSF during Therapy for Meningitis.- 4.1. Need for Cidal Concentrations in CSF.- 4.2. Experimental Demonstration.- 4.3. Clinical Evidence.- 4.4. Optimum CSF Concentrations of Antimicrobial Agents.- 5. Factors Affecting Penetration of Antimicrobial Agents into CSF.- 5.1. Physicochemical Properties.- 5.2. Transport Mechanisms and Inhibitors.- 5.3. Experimental Methodology and Drug Kinetics.- 5.4. Osmotic Disruption of the Blood-Brain Barrier.- 5.5. Corticosteroid Therapy.- 6. Penetration of Antimicrobial Agents into CSF.- 6.1. Overview.- 6.2. ?-Lactam Antibiotics.- 6.3. Aminoglycoside Antibiotics.- 6.4. Chloramphenicol.- 6.5. Lincosamide Antibiotics.- 6.6. Tetracycline Antibiotics.- 6.7. Metronidazole.- 6.8. Sulfonamides and Trimethoprim.- 6.9. Vancomycin.- 6.10. Macrolide Antibiotics.- 6.11. Polypeptide Antibiotics.- 6.12. Antituberculous Agents.- 6.13. Antifungal Agents.- 7. Therapy for Meningitis.- 8. Summary and Conclusions.- References.- 24. Viral Infections and the Blood-Brain Barrier.- 1. Introduction.- 2. Mechanisms of Viral Passage across the Blood-Brain Barrier.- 2.1. The Neural Route.- 2.2. The Olfactory Route.- 2.3. The Hematogenous Route.- 3. Immune Responses to Viral Infection of the CNS.- 3.1. Local Antibody Synthesis.- 3.2. Effects of Immunosuppression.- 4. Blood-Brain Barrier Alterations in Experimental CNS Viral Infections.- 4.1. Sindbis Virus.- 4.2. Herpes Simplex Virus.- 4.3. Lymphocytic Choriomeningitis Virus.- 5. Blood-Brain Barrier Alterations in Human CNS Viral Infections.- 5.1. Herpes Simplex Encephalitis.- 5.2. AIDS Dementia Complex.- 6. CNS Antiviral Therapy.- 6.1. Nucleoside Analogues.- 6.2. Interferons.- 6.3. Immunoglobulins.- 7. Summary.- References.- 25. CNS Lupus and the Blood-Brain Barrier.- 1. Introduction.- 2. Neuropsychiatric Manifestations in Systemic Lupus Erythematosus.- 3. The Blood-Brain Barrier in CNS Lupus.- 3.1. The Blood-Brain Barrier and Blood-CSF Barrier.- 3.2. Neuropathology: Vascular Lesions.- 3.3. Blood-Brain Barrier Permeability Changes.- 4. Conclusions.- 4.1. Speculations and Questions.- 4.2. Summary.- References.- 26. Cerebrovascular Disease and the Blood-Brain Barrier.- 1. Introduction.- 2. Biochemistry of Ischemia.- 3.Eicosanoids, Cerebrovascular Disease, and the Blood-Brain Barrier.- 4. Evaluation of Blood-Brain Barrier Permeability.- 5. Cerebral Ischemia and Cerebral Infarction.- 5.1. Middle Cerebral Artery Occlusion.- 5.2. Common Carotid Artery Occlusion.- 5.3. Global Ischemia.- 5.4. Clinical Perspective.- 6. Hypoxia/Anoxia.- 7. Embolization.- 8. Hypertension.- 9. Spontaneous Intracerebral Hemorrhage.- 10. Subarachnoid Hemorrhage.- 11. Vascular Malformations.- 12. Cerebral Venous Disease.- 13. Neonatal Cerebral Injury.- 14. Radiation Cerebral Damage.- 15. Other Cerebrovascular Conditions.- 15.1. Diabetes.- 15.2. Cerebral Arteritides.- 15.3. Migraine.- 15.4. Substance Abuse Vasculopathy.- 15.5. Binswanger Subacute Arteriosclerotic Encephalopathy.- 16. Conclusion.- References.- 27. Epileptic Seizures and the Blood-Brain Barrier.- 1. General Considerations Concerning the Integrity of the Blood-Brain Barrier.- 2. BBB Dysfunction during Seizures.- 2.1. Animal Studies.- 2.2. Relationship between CBF and the BBB during Seizures.- 2.3. BBB Dysfunction during Seizures: Mechanical and Chemical Determinants.- 2.4. BBB, CBF, and Regional Differences.- 2.5. Human Studies: Dynamic Findings.- 3. Clinical Implications.- References.- 28. Metabolic Disturbances of the Blood-Brain Barrier with Special Emphasis on Glucose and Amino Acid Transport.- 1. Glucose.- 1.1. General Consideration of Transport Mechanisms for Glucose across the Blood-Brain Barrier.- 1.2. Glucose Carrier Transport.- 1.3. Insulin Effect.- 1.4. Influence of Blood Flow and pH.- 1.5. Induction of Transport.- 1.6. Glucose Transfer in Galactosemia.- 1.7. Glucose Transfer during Ethanol Intoxication and Withdrawal.- 1.8. Glucose Transfer in Meningitis.- 2. Amino Acids.- 2.1. General Considerations of Transport of Amino Acids across the Blood-Brain Barrier.- 2.2. Role of a BBB in Hepatic Encephalopathy.- 2.3. Aminoacidurias.- 3. Miscellaneous.- 3.1. Kernicterus.- 3.2. Uremic Encephalopathy.- 3.3. Decompression Sickness.- 3.4. Disturbances of Electrolyte, Acid-Base, and Water Balance.- 3.5. Heavy Metals and the Blood-Brain Barrier.- 4. Summary.- 4.1. Glucose.- 4.2. Amino Acids.- 4.3. Miscellaneous.- References.- 29. Implantable Pumps to Deliver Drugs Directly into the CNS.- 1. Introduction.- 2. Rationale for Directly Bypassing the Blood-Brain Barrier.- 2.1. Drugs That Do Not Naturally Cross the Blood-Brain Barrier.- 2.2. Localization of Drug Effect.- 2.3. Avoidance of the Circulatory System.- 3. Applications of Chronic Central Nervous System Infusion.- 3.1. Intrathecal Morphine for Pain Relief in Cancer Patients.- 3.2. Intrathecal Baclofen for Spinal Cord Spasticity.- 3.3. CSF and Interstitial Infusion of Anticancer Drugs for Malignant Brain Tumors.- 3.4. Cholinergic Infusion for Alzheimer Disease.- 4. Future Clinical Applications.- 5. Summary.- References.