Table of Contents

1 Disorders of Sphingolipid Metabolism.- I. Introduction.- II. Chemistry, Metabolism, and Distribution of Sphingolipids.- A. Chemistry.- B. Metabolism.- C. Distribution.- III. Individual Sphingolipidoses.- A. Sphingomyelinosis (Niemann-Pick Disease).- B. Glucosylceramide Lipidosis (Gaucher's Disease).- C. Leukodystrophies.- D. Lactosylceramide Lipidosis.- E. Trihexosylceramide Lipidosis (Fabry's Disease).- F. Gangliosidoses.- G. Miscellaneous Disorders.- IV. Summary and Concluding Remarks.- References.- 2 Disorders of the Cerebral Circulation.- I. Introduction.- II. Methods for Study of the Cerebral Circulation.- A. Cerebral Blood Flow and Cerebral Vascular Resistance.- B. Cerebral Blood Vessels.- III. Regulation of the Cerebral Circulation.- A. Regulatory Responses of Vascular Caliber and Blood Flow.- B. Vascular, Neural, and Humoral Mechanisms for the Regulation of the Cerebral Circulation.- IV. Dysfunction of Regulatory Mechanisms.- A. Effects of Ischemia.- B. Effects of Hypoxemia and Hyperoxemia.- C. Effects of Increased Intracranial Pressure.- D. Effects of Sustained Hypertension.- E. Effects of Miscellaneous Factors.- V. Intravascular Phenomena.- A. Normal Cerebral Circulation.- B. Abnormal Circulatory States.- VI. Secondary Effects of Disturbed Regulation.- A. Hyperemia and Venous Hyperoxemia.- B. Cerebral Edema.- C. "Diaschisis" and Generalized Decreases of CBF.- D. Cardiac and Systemic Effects.- VII. Conclusion.- References.- 3 Effects of Narcotic Analgesics on Brain function.- I. Introduction.- II. Physiological Effects of Narcotic Analgesics.- A. Pharmacology of Narcotics.- B. Alterations of Lower Brain Stem Functions by Narcotics.- C. Alterations of Subcortical Functions by Narcotics.- D. Alterations of Cortical Functions by Narcotics.- III. Metabolism of Narcotic Analgesics in the Nervous System.- A. Penetration and Distribution in the Nervous System.- B. Blood-Brain Barrier to Narcotics.- C. Biotransformations of Narcotics.- IV. Biochemical Responses to Narcotics.- A. General Effects.- B. Pituitary-Adrenal Effects.- C. Role of the Biogenic Amines and Acetylcholine.- D. Localization of Drug Responses.- E. Tolerance to Biochemical Responses.- V. Electroencephalography.- A. Electroencephalography in Experimental Animals.- B. Electroencephalography in Man.- VI. Theories on the Mechanism of Addiction to Narcotics.- VII. Summary and Conclusions.- References.- 4 Genetic Disorders of Brain Development: Animal Models.- I. Introduction.- II. Chromosomal Organization in Eukaryotes.- A. Structural Genes.- B. Regulatory Genes.- C. Architectural Genes.- D. Temporal Genes.- III. Development of the CNS.- A. Formation of the Neural Tube.- B. Cell Proliferation.- C. Cell Migration.- D. Differentiation of Neurons.- E. Differentiation of Oligodendrocytes: Myelination.- IV. Genetic Disorders of Brain Development.- A. Abnormal Induction of the Neural Tube.- B. Abnormal Formation of the Neural Crest.- C. Abnormal Folding of the Neural Tube.- D. Abnormal Induction of Sensory Organs.- E. Abnormal Migration and Alignment of Cortical Cells.- F. Disorders of Myelin Formation.- G. Metabolic Disorders Which May Act on Different Levels of Development.- H. Increased Death Rate of Cells.- I. Genetic Mutations Affecting Brain Metabolism.- V. Prevention of Brain Dysfunction.- References.- 5 Experimental Allergic Encephalomyelitis.- I. Introduction.- II. Historical Background.- A. Clinical "Accidents" Related to Injections of CNS Tissue.- B. Induction of EAE in Laboratory Animals.- III. Identification of Specific Encephalitogenic Components of CNS Tissue.- A. Early Studies.- B. Bioassay.- C. Isolation of the Encephalitogen and Its Characterization as Myelin Basic Protein.- D. Structural Studies.- E. Species Relationships.- IV. Pathogenesis of EAE.- A. Delayed Hypersensitivity.- B. Role of Serum Antibody.- V. Possible Relationship of EAE to Human Demyelinative Disorders.- Acknowledgments.- References.- 6 Disorders of Fatty Acids.- I. Introduction.- II. Fatty Acids in Normal Brain and Nerve.- A. Distribution and Composition of Fatty Acids in Brain and Nerve.- B. Origin of Brain Fatty Acids.- III. Phytanic Acid Storage Disease (Refsum's Disease).- A. Clinical and Biochemical Abnormalities.- B. Pathophysiology of Phytanic Acid Storage Disease.- IV. Disorders with Storage of Ceroid.- V. Other Storage Disorders.- VI. Demyelination of Known Etiology.- VII. Multiple Sclerosis.- A. Abnormalities in Fatty Acids in Multiple Sclerosis.- B. Relation of the Analytical Findings to the Clinical Syndrome.- VIII. Other Human Disorders.- IX. Animal Disorders.- X. Criteria for Establishing Primary Disorders of Cerebral Fatty Acid Metabolism.- References.- 7 Bilirubin Encephalopathy.- I. Introduction and Historical Perspective.- II. Chemistry and Metabolism of Bilirubin with Special Note of Variations Seen in the Newborn Period.- III. Protein Binding of Bilirubin.- A. Influence of Molar Ratios and pH on Binding of Bilirubin and Albumin.- B. Other Factors Which Affect Binding of Bilirubin by Albumin.- IV. Problems Hampering Research.- V. Pathological Lesion of Bilirubin Encephalopathy.- A. Gross Observations.- B. Observations with Light Microscopy.- C. Observations with Electron Microscopy.- VI. Extraneural Pathological Lesions Induced by Bilirubin.- VII. Metabolic Lesions Induced by Bilirubin.- A. Effects of Bilirubin on Tissue Respiration.- B. Effects of Bilirubin on Lipids.- C. Effects of Bilirubin on Cell Membrane Systems.- D. Other Metabolic Reactions.- VIII. Why Is Brain Damage the Main Pathological Phenomenon Induced by Bilirubin?.- References.- 8 The Action of Thyroid Hormones and Their Influence on Brain Development and function.- I. Introduction.- A. Chemical Nature of Thyroid Hormones.- B. General Biological and Biochemical Effects of Thyroid Hormones.- II. General Role of Thyroid Hormones in the Structural and Functional Maturation of the Nervous System.- A. Morphology.- B. Electrical Activity.- C. Behavior and Learning in Experimental Animals.- D. Maturation of Brain Function in Man.- E. Conclusions Regarding the Role of Thyroid Hormones in the Functional Development of the Nervous System.- III. Biochemical and Metabolic Effects of Thyroid Hormones in Nervous Tissues.- A. Energy Exchange.- B. Lipid Synthesis.- C. Miscellaneous Enzymes.- D. Nucleic Acid and Protein Synthesis.- References.- 9 Biology of the Striatum.- I. Introduction.- II. Role of the Striatum in Motility.- A. "Filter" Mechanism in Tone Control.- B. "Set" Function of the Striatum.- C. Definition of Akinesia.- D. "Trigger" Function of the Striatum.- E. The "Drive" Mechanism.- III. Role of the Striatum in Mental Function.- IV. Role of the Striatum in Autonomic Functions.- A. Neuronal Regulation of Dopamine Metabolism.- B. Hormonal Regulation of Dopamine Metabolism.- V. Conclusions.- References.- 10 Pathophysiology of Central Nervous System Regulation of Anterior Pituitary function.- I. Introduction.- A. Experimental Approaches Utilized.- B. Principles of Neuroendocrine Regulation.- II. Concept of Endocrine Regulation Via Releasing Hormones of Neural Origin.- A. Anatomical Factors.- B. Chemical Nature of Hypothalamic Releasing Hormones.- C. Mode of Secretion of Hypothalamic Releasing Hormones.- D. Mode of Action of Hypothalamic Releasing Hormones.- E. Neurotransmitters Involved in the Release of Hypophysiotropic Releasing Hormones.- F. Feedback Regulation of Pituitary Hormone Secretion.- III. Factors Involved in the Periodic Release of Pituitary Hormones.- A. Introduction.- B. Specific Examples of Periodic Hormone Release.- IV. Effect of Neonatal Hormonal Milieu on Neuroendocrine Control Mechanisms.- A. Concept of a Critical Period.- B. Gonadal Steroids.- C. Adrenal Steroids.- D. Thyroid Hormone.- V. Clinical Correlates.- A. Testing for Neuroendocrine (Hypothalamic) Dysfunction.- B. Endocrine Disorders in CNS Disease.- C. Clinical Use of Releasing Hormones.- References.- of Volume 1.- Articles Planned for Future Volumes.