Biology of Brain Dysfunction

1 Pathophysiology of Perinatal Hypoxic-Ischemic Brain Damage.- I. Introduction.- II. Human Perinatal Hypoxia-Ischemia.- A. Definitions.- B. Predisposing Factors.- C. Perinatal Mortality and Morbidity.- III. Neuropathology of Perinatal Hypoxia-Ischemia.- IV. Perinatal Central Nervous System Development.- A. Cerebrovascular Development.- B. Cerebral Energy Transformations in Developing Brain.- V. Experimental Approaches to Perinatal Hypoxia-Ischemia.- A. Perinatal Resistance in Hypoxia and Ischemia.- B. Methods of Producing Hypoxia and Cerebral Ischemia.- C. Effects of Hypoxia and Ischemia on the Brain.- D. Effects of Hypoxia on the Heart.- E. Factors Modifying the Response to Hypoxia.- VI. Conclusions.- References.- 2 Pathogenesis of Brain Dysfunction in Inborn Errors of Amino Acid Metabolism.- I. Introduction.- A. The Metabolic Sequelae of an Inborn Error of Amino Acid Metabolism.- B. Lines of Evidence Bearing on the Neurological Effects of These Metabolic Sequelae.- C. The Free Amino Acid Pools of the Nervous System.- D. Abnormalities in the Concentrations of Free Amino Acids and Metabolites in the Brain of Patients with Inborn Errors of Amino Acid Metabolism.- II. Effects of Metabolic Sequelae on the Fluxes and Transport of Amino Acids.- A. Amino Acid Fluxes.- B. Alterations of Amino Acid Transport.- III. Effects of Metabolic Sequelae on Synthesis of Protein in Brain.- IV. Effects of Metabolie Sequelae on Substances Affecting Neurotransmission in Brain.- A. Metabolism of Putative Amino Acid Transmitters.- B. Metabolism of Catecholamines.- C. Metabolism of 5-Hydroxytryptamine.- V. Effects of Metabolie Sequelae on Carbohydrate Metabolism and Energy Utilization.- VI. Effects of Metabolie Sequelae on Synthesis of Lipids and Myelin.- VII. Comments and Conclusions.- A. Evidence for Theories of Pathogenesis.- B. The Threshold for Neurological Deficit.- References.- 3 Disorders of Organic Acid Metabolism.- I. Introduction.- II. Inborn Errors of Leucine Metabolism.- A. Isovaleric Acidemia.- B. ?-Methylcrotonyl CoA Carboxylase Deficiency.- III. Inborn Errors of Isoleucine and Valine Metabolism.- A. ?-Methylacetoacetyl CoA Thiolase Deficiency.- B. Propionic Acidemia.- C. Methylmalonic Acidemia.- IV. Inborn Errors of Metabolism of Other Organic Acids.- A. Pyroglutamic Aciduria.- B. Congenital Medium-Chain Dicarboxylic Aciduria.- C. Glutaric Acidemia.- V. Inborn Errors of Pyruvate Metabolism.- A. Pyruvate Metabolism and Its Metabolie Regulations.- B. Pyruvate Carboxylase Deficiency.- C. Pyruvate Decarboxylase Deficiency.- VI. Disorders of Organic Acid Metabolism Induced by Natural Toxin.- A. Jamaican Vomiting Sickness.- References.- 4 Biological Aspects of Affective Psychoses.- I. Introduction.- II. Clinical Features.- III. The Biogenic Amine Hypothesis.- IV. Indoleamines in Affective Disorders.- A. Urinary Studies.- B. Cerebrospinal Fluid Studies.- C. 5-HIAA and 5-HT in the Brains of Depressed Suicidal Patients.- D. The Effects of Tryptophan and 5-HT Antagonists in Affective Disorders.- V. Lithium and Affective Disorders.- VI. Catecholamines and Affective Disorders.- A. Urinary Studies.- B. Cerebrospinal Fluid Studies.- C. The Effect of l-Dopa on Mood.- D. Effects of ?-Methylparatyrosine.- E. Enzymatic Studies.- F. Electroconvulsive Therapy (ECT).- G. Cholinergic-Adrenergic Interactions.- VII. Neuroendocrine Function in Affective Disorders.- A. Growth Hormone.- B. Prolactin.- C. ACTH and Cortisol.- D. Thyroid.- E. Sex Hormones.- VIII. Conclusions.- References.- 5 Wilson’s Disease.- I. Copper Metabolism.- II. Copper Toxicity.- III. An Inherited Abnormality of Copper Metabolism: Wilson’s Disease.- A. Pathology.- B. Pathological Physiology.- C. Clinical Aspects of Wilson’s Disease in the Central Nervous System.- D. Treatment.- E. Assessment of Current Knowledge of the Biochemical Lesion in Wilson’s Disease.- References.- 6 Pathogenesis of Slow Infections of the Central Nervous System.- I. Introduction.- II. Slow Virus Subacute Spongiform Encephalopathies.- A. General.- B. A Model System for Slow Virus Subacute Spongiform Encephalopathies: Scrapie.- C. Other Subacute Spongiform Encephalopathies.- D. Conclusion.- III. Slow Viral Encephalomyelitides.- A. General.- B. Subacute Sclerosing Panencephalities.- C. Other Slow Encephalomyelitides.- D. Conclusion.- References.- 7 Pathogenesis of Intrauterine Infections of the Brain.- I. Introduction.- II. Factors Required for the Initiation of Intrauterine Brain Infection.- A. Maternal Infection with Fetal Transmission.- B. Susceptible Stage of Gestation.- III. Infections Affecting the Fetal or Newborn Central Nervous System.- A. Naturally Occurring Infections in Man.- B. Naturally Occurring and Experimentally Induced Infections in Lower Animals.- IV. Possible Effector Mechanisms of Virus-Mediated Damage to the Developing Brain.- A. Generalized Placental and Fetal Infection.- B. Vasculitis.- C. Predilection for Discreet CNS Cell Populations of Either Immature or Differentiated Cell Types.- D. Chromosomal Injury.- E. Immunological Mechanisms.- F. Indirect Injury.- V. Fetal Immunological Response.- VI. Interferons.- VII. Discussion.- References.- 8 Ionizing Radiations and the Nervous System.- I. Introduction.- II. Some Radiobiological Considerations.- III. Developing Organisms.- A. Experimental Studies.- B. Effects in Man.- IV. The Adult.- A. Structural Changes.- B. Functional Changes.- References.- 9 Brain Dysfunction in Congenital Malformations of the Nervous System.- I. Introduction.- II. Dysraphic States.- A. Anencephaly.- B. Cranial Dysraphism Other Than Anencephaly.- III. Cerebral Ageneses and Hypoplasias.- A. Hypoplasia of the Cerebral Hemispheres.- B. Arhinencephaly.- C. Absence of the Corpus Callosum.- D. Agenesis of the Septum Pellucidum.- E. Absence or Hypoplasia of the Cerebellum.- F. Agenesis or Hypoplasia of Cranial Nerve Nuclei.- IV. Dysgenesis of the Cerebral Structures.- A. Lyssencephaly or Agyria.- B. Cerebral Polymicrogyria.- C. Cerebellar Polymicrogyria.- D. Heterotopia.- E. Minor Architectural Anomalies of the Cerebral Cortex.- F. Congenital Hyperplasia of the Brain, or Megalencephaly.- V. Developmental Cyst Formation.- A. Cavum Septi Pellucidi.- B. Developmental Porencephaly.- VI. Congenital Hydrocephalus and Hydranencephaly.- A. Congenital Hydrocephalus.- B. Hydranencephaly.- VII. Synopsis.- References.- 10 Pathogenesis of Brain Dysfunction in Deficiency of Thiamine, Riboflavin, Pantothenic Acid, or Vitamin B6.- I. Introduction.- II. Thiamine Deficiency.- A. Introduction.- B. Manifestations of Thiamine Deficiency.- C. Biochemical Changes in Thiamine Deficiency.- D. Summary.- III. Riboflavin Deficiency.- A. Introduction.- B. Manifestations of Riboflavin Deficiency.- C. Biochemical Changes in Riboflavin Deficiency.- D. Summary.- IV. Pantothenic Acid Deficiency.- A. Introduction.- B. Manifestations of Pantothenic Acid Deficiency.- C. Biochemical Changes in Pantothenic Acid Deficiency.- D. Summary.- V. Vitamin B6 Deficiency.- A. Introduction.- B. Manifestations of Vitamin B6 Deficiency.- C. Biochemical Changes in Vitamin B6 Deficiency.- D. Summary.- References.