E-Book, Englisch, 268 Seiten
Haddad / Yu Brain Hypoxia and Ischemia
1. Auflage 2009
ISBN: 978-1-60327-579-8
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark
E-Book, Englisch, 268 Seiten
Reihe: Contemporary Clinical Neuroscience
ISBN: 978-1-60327-579-8
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark
explores the various aspects of cell death and survival that are crucial for understanding the basic mechanisms underlying brain hypoxia and ischemia. Chapters focus on a panorama of issues including the role of ion channels/transporters, mitochondria and apoptotic mechanisms, the roles of glutamate/NMDA, mechanisms in penumbral cells and the importance of intermittent hypoxia and gene regulation under these stressful conditions. The volume explores findings from both mammalian and invertebrate model systems and their applicability to human systems and diseases. Careful consideration is also given to differences in hypoxia and ischemia across development.
This volume aims to increase the understanding of these mechanisms and to stimulate research on better diagnosis and treatment of diseases that afflict the brain and potentially other organs when O levels are dysregulated. is designed for neuroscientists, clinicians and medical/graduate students for use in both basic research and clinical practice.
Autoren/Hrsg.
Weitere Infos & Material
1;Brain Hypoxia and Ischemia;2
1.1;Title Page;3
1.2;Copyright Page;4
1.3;Preface;5
1.4;Contents;7
1.5;Contributors;9
1.6;Part I: Ion Channels, Transporters and Excitotoxicity;12
1.6.1;Chapter 1;13
1.6.1.1;Regulation of Vulnerability to NMDA Excitotoxicity During Postnatal Maturation;13
1.6.1.1.1;1.1 Postnatal Maturation Alters the Vulnerability of the Brain to Acute Injury;13
1.6.1.1.1.1;1.1.1 Vulnerability to Hypoxia-Ischemia Changes During Postnatal Development;13
1.6.1.1.1.2;1.1.2 Vulnerability to Excitotoxicity During Postnatal Development;15
1.6.1.1.1.3;1.1.3 Increases in Vulnerability of Cultured Neurons with Increasing Time In Vitro;17
1.6.1.1.2;1.2 Developmental Regulation of NMDA Receptor Expression;18
1.6.1.1.2.1;1.2.1 NMDA Receptor Subunits and Functional Properties;18
1.6.1.1.2.2;1.2.2 Developmental Regulation of NMDA Receptor Subunit Expression;19
1.6.1.1.2.3;1.2.3 Contribution of NR2A and NR2B Subunits to Excitotoxicity;20
1.6.1.1.2.4;1.2.4 Role of NR2A and NR2B Subunits in Regulating Developmental Regulation of Vulnerabilityto Excito toxicity;21
1.6.1.1.2.5;1.2.5 Role of Synaptic and Extrasynaptic NMDA Receptors;22
1.6.1.1.2.6;1.2.6 NMDA Receptor Desensitization During Development;23
1.6.1.1.3;1.3 Role of Ongoing Synaptic Activity and NMDA Release;24
1.6.1.1.4;1.4 Nitric Oxide;25
1.6.1.1.4.1;1.4.1 Nitric Oxide as a Neurotoxin;25
1.6.1.1.4.2;1.4.2 Developmental Regulation of NOS Expression and NO Production;25
1.6.1.1.4.3;1.4.3 Mitochondrial Nitric Oxide Production: A Mediator of Decreased Vulnerability in the Neonatal Period;26
1.6.1.1.5;References;28
1.6.2;Chapter 2;35
1.6.2.1;Acidosis, Acid-Sensing Ion Channels, and Glutamate Receptor-Independent Neuronal Injury;35
1.6.2.1.1;2.1 Glutamate Excitotoxicity;36
1.6.2.1.2;2.2 Brain Acidosis Activates Acid-Sensing Ion Channels;36
1.6.2.1.2.1;2.2.1 Brain Acidosis;36
1.6.2.1.2.2;2.2.2 Acidosis Induces Neuronal Injury;37
1.6.2.1.2.3;2.2.3 Acid-Sensing Ion Channels;37
1.6.2.1.2.4;2.2.4 Tissue Distribution and Electrophysiological Properties of ASICs;38
1.6.2.1.3;2.3 Pharmacology of ASICs;39
1.6.2.1.3.1;2.3.1 Amiloride;39
1.6.2.1.3.2;2.3.2 A-317567;40
1.6.2.1.3.3;2.3.3 Psalmotoxin 1 (PcTX1);40
1.6.2.1.3.4;2.3.4 APETx2;40
1.6.2.1.3.5;2.3.5 Nonsteroid Anti-inflammatory Drugs (NSAIDs);41
1.6.2.1.4;2.4 Modulation of ASIC Activity by Ischemia-Related Signals;41
1.6.2.1.4.1;2.4.1 Proteases;41
1.6.2.1.4.2;2.4.2 Arachidonic Acid;42
1.6.2.1.4.3;2.4.3 Lactate;42
1.6.2.1.4.4;2.4.4 Glucose;43
1.6.2.1.5;2.5 Activation of ASICs Induces Neuronal Excitation and Increased Intracellular Ca2+;43
1.6.2.1.6;2.6 ASIC1a Activation Plays an Important Role in Acidosis-Induced Neuronal Injury;44
1.6.2.1.7;2.7 Evidence of a Developmental Change of ASICs;45
1.6.2.1.8;References;45
1.6.3;Chapter 3;52
1.6.3.1;Brain Ischemia and Neuronal Excitability;52
1.6.3.1.1;3.1 Excitatory Neurotransmission After Ischemia;53
1.6.3.1.2;3.2 Voltage-Dependent Potassium Currents After Ischemia;56
1.6.3.1.3;3.3 Conclusion;58
1.6.3.1.4;References;59
1.6.4;Chapter 4;62
1.6.4.1;Critical Roles of the Na+/K+-ATPase in Apoptosis and CNS Diseases;62
1.6.4.1.1;4.1 Introduction;62
1.6.4.1.1.1;4.1.1 Molecular Structure of the Na+/K+-ATPase;63
1.6.4.1.1.1.1;4.1.1.1 Structure and Function of alpha Subunit;63
1.6.4.1.1.1.2;4.1.1.2 Structure and Function of beta Subunit;64
1.6.4.1.1.1.3;4.1.1.3 Structure and Function of gamma Subunit (FXYD Proteins);64
1.6.4.1.1.2;4.1.2 Physiological Function of the Na+/K+-ATPase;65
1.6.4.1.1.3;4.1.3 Physiologic Regulation of the Na+/K+-ATPase;66
1.6.4.1.1.3.1;4.1.3.1 Dual Effects of Ouabain and Cardiac Glycosides;66
1.6.4.1.1.3.2;4.1.3.2 Ouabain-Mediated Signal Transduction;66
1.6.4.1.1.3.3;4.1.3.3 Protein Kinase Regulation of the Na+/K+-ATPase;67
1.6.4.1.1.3.4;4.1.3.4 Src Family Kinases as Regulators of the Na+, K+-ATPase;67
1.6.4.1.1.3.5;4.1.3.5 AMP-Kinase Regulation of Na+/K+-ATPase;68
1.6.4.1.2;4.2 The Na+/K+-ATPase and Cell Death;68
1.6.4.1.2.1;4.2.1 Regulation of the Na+/K+-ATPase Under Pathological Conditions;68
1.6.4.1.2.1.1;4.2.1.1 Hypoxic and Ischemic Regulation of the Na+/K+-ATPase;68
1.6.4.1.2.2;4.2.2 K+ Homeostasis and Apoptosis;70
1.6.4.1.2.3;4.2.3 Na+/K+-ATPase, Apoptosis, and Hybrid Cell Death;72
1.6.4.1.2.3.1;4.2.3.1 Synergistic Effects of Low Concentrations of Ouabain and Sublethal Apoptotic Insults;73
1.6.4.1.2.3.2;4.2.3.2 Blocking Na+/K+-ATPase Induces Hybrid Cell Death with Both Apoptotic and Necrotic Features;73
1.6.4.1.3;4.3 Neuronal Function of the Na+/K+-ATPase and Roles in CNS Diseases;74
1.6.4.1.3.1;4.3.1 Emerging Neuronal Functions of the Na+/K+-ATPase;74
1.6.4.1.3.1.1;4.3.1.1 The Na+/K+-ATPase as a Receptor for Agrin;74
1.6.4.1.3.1.2;4.3.1.2 Na+/K+-ATPase alpha Subunit Knockout Phenotypes;75
1.6.4.1.3.2;4.3.2 The Na+/K+-ATPase and CNS Diseases;75
1.6.4.1.3.2.1;4.3.2.1 Stroke;75
1.6.4.1.3.2.2;4.3.2.2 Alzheimer Disease/Alzheimer’s Disease?;76
1.6.4.1.3.2.3;4.3.2.3 Parkinson’s Disease;76
1.6.4.1.3.2.4;4.3.2.4 Rapid Onset Dystonia-Parkinsonism;77
1.6.4.1.3.2.5;4.3.2.5 Bipolar Disorder;77
1.6.4.1.3.2.6;4.3.2.6 Familial Hemiplegic Migraine Type II;78
1.6.4.1.4;4.4 Na+/K+-ATPases as Drug Targets;78
1.6.4.1.4.1;4.4.1 Naturally Occurring Na+/K+-ATPase Inhibitors;78
1.6.4.1.4.2;4.4.2 Na+/K+-ATPase as Therapeutics for Cancer;79
1.6.4.1.4.3;4.4.3 Targeting the Na+/K+-ATPase for Cytoprotection;79
1.6.4.1.5;4.5 Conclusion;80
1.6.4.1.6;References;80
1.6.5;Chapter 5;88
1.6.5.1;Emerging Role of Water Channels in Regulating Cellular Volume During Oxygen Deprivation and Cell Death;88
1.6.5.1.1;5.1 Volume Regulatory Mechanisms;88
1.6.5.1.2;5.2 Properties of AQP and Their Neuronal Expression;89
1.6.5.1.2.1;5.2.1 AQP in the Brain;91
1.6.5.1.3;5.3 Changes in Aquaporin Expression During Hypoxia and Ischemia;92
1.6.5.1.3.1;5.3.1 Nonapoptotic Roles for AQP During Hypoxia/Ischemia;92
1.6.5.1.4;5.4 AVD: Role and Significance of AQP;94
1.6.5.1.5;5.5 Regulation of Aquaporin Expression and Function After (and Before) the AVD;95
1.6.5.1.6;5.6 Colocalization of AQP and Potassium Channels;97
1.6.5.1.7;5.7 Concluding Remarks;99
1.6.5.1.8;References;99
1.6.6;Chapter 6;106
1.6.6.1;A Zinc–Potassium Continuum in Neuronal Apoptosis;106
1.6.6.1.1;6.1 Introduction;106
1.6.6.1.2;6.2 Role of Zn2+ in Neuronal Injury;107
1.6.6.1.3;6.3 Mechanism of Zn2+ Neurotoxicity;108
1.6.6.1.4;6.4 Intracellular Release of Zn2+;108
1.6.6.1.5;6.5 Cell Death Signaling Events Following Liberation of Intracellular Zn2+;109
1.6.6.1.6;6.6 Potassium Efflux and Apoptosis;112
1.6.6.1.7;6.7 The Zinc–Potassium Continuum in Ischemia;113
1.6.6.1.8;6.8 Alternative Zn2+ Signaling Pathways;114
1.6.6.1.9;6.9 Intracellular Zn2+ Release in Chronic Models of Neurodegeneration;115
1.6.6.1.10;6.10 Concluding Remarks;116
1.6.6.1.11;References;117
1.6.7;Chapter 7;125
1.6.7.1;Mitochondrial Ion Channels in Ischemic Brain;125
1.6.7.1.1;7.1 Introduction;126
1.6.7.1.2;7.2 Role of VDAC in Mitochondrial Function;126
1.6.7.1.3;7.3 Biophysical Characteristics of VDAC;127
1.6.7.1.4;7.4 Control of Metabolism by VDAC;128
1.6.7.1.5;7.5 BCL-2 Family Ion Channels: Role in Programmed Cell Death in Neurons;129
1.6.7.1.6;7.6 Actions of BCL-2 Family Proteins Are Regulated by Binding Partners;130
1.6.7.1.7;7.7 BCL-2 Family Proteins Function as Ion Channels;131
1.6.7.1.8;7.8 Recordings of BCL-2 Family Proteins In Vivo;132
1.6.7.1.9;7.9 Endogenous Death Channels Produced by BAX-Containing Protein Complexes;134
1.6.7.1.10;7.10 Interaction of VDAC with BCL-2 Family Proteins;134
1.6.7.1.11;7.11 VDAC and Apoptosis;135
1.6.7.1.12;7.12 Interaction of VDAC with BCL-2 Family Members;135
1.6.7.1.13;7.13 Interactions of VDAC with BCL-xL;135
1.6.7.1.14;7.14 BCL-xL Interaction with VDAC in Mitochondria of Live Neurons;137
1.6.7.1.15;7.15 VDAC2 Inhibits Apoptosis;137
1.6.7.1.16;7.16 Mitochondrial Inner Membrane Channels;138
1.6.7.1.17;7.17 Energy dependence of Mitochondrial Calcium Accumulation;138
1.6.7.1.18;7.18 Voltage-Dependent Inner Membrane Channels: The Calcium Uniporter;139
1.6.7.1.19;7.19 Other Inner Membrane Conductances: Mitoplast Recording Technique;140
1.6.7.1.20;7.20 Channel Activity Correlated with Permeability Transition: The Mitochondrial Permeability Pore (mPTP);140
1.6.7.1.21;7.21 Complex of Channels Exists at Contact Points Between Outer and Inner Membranes;142
1.6.7.1.22;7.22 Fundamental Events During Ischemia;143
1.6.7.1.23;7.23 Cellular Events During Ischemia-Excitotoxicity;144
1.6.7.1.24;7.24 Role of Oxygen-Free Radicals in Ischemic Neuronal Damage;145
1.6.7.1.25;7.25 BCL-2 Family Proteins in Ischemic Neuronal Damage;146
1.6.7.1.26;7.26 Large Channels of Mitochondria from Postischemic Hippocampal CA1 Neurons;147
1.6.7.1.27;7.27 Large Channel Activity Associated with VDAC;148
1.6.7.1.28;7.28 Large Zn2+-Activated Channels in Postischemic Mitochondria;148
1.6.7.1.29;7.29 Ischemic Tolerance and Mitochondrial Ion Channel Activity;149
1.6.7.1.30;7.30 Mito K ATP;150
1.6.7.1.31;7.31 Mito KCa;150
1.6.7.1.32;7.32 Conclusions;151
1.6.7.1.33;References;151
1.7;Part II: Reactive Oxygen Species, and Gene Expression to Behavior;159
1.7.1;Chapter 8;160
1.7.1.1;Perinatal Panencephalopathy in Premature Infants: Is It Due to Hypoxia-Ischemia?;160
1.7.1.1.1;8.1 Introduction;160
1.7.1.1.2;8.2 The Neuropathology of PPPI;161
1.7.1.1.3;8.3 Strategy Toward Establishing the Causative Role for Hypoxia-Ischemia in PPPI;170
1.7.1.1.4;8.4 Evidence for the Causative Role for Hypoxia-Ischemia in PVL Based upon Human Clinical Studies;173
1.7.1.1.5;8.5 Evidence for the Causative Role for Hypoxia-Ischemia in PVL Based upon Human Pathologic Studies;176
1.7.1.1.6;8.6 Evidence for the Causative Role for Hypoxia-Ischemia in PVL Based upon Pathologic Studies in Animal Models;179
1.7.1.1.7;8.7 Intrinsic Vulnerability of the Cerebral White Matter of the Premature Newborn to Hypoxia-Ischemia;180
1.7.1.1.8;8.8 The Causative Role of Synergistic Factors in PVL;181
1.7.1.1.9;8.9 The Potential Role of Cumulative Hypoxic-Ischemic Insults in PPPI;184
1.7.1.1.10;8.10 Conclusions;184
1.7.1.1.11;References;185
1.7.2;Chapter 9;193
1.7.2.1;Effects of Intermittent Hypoxia on Neurological Function;193
1.7.2.1.1;9.1 Intermittent Hypoxia;193
1.7.2.1.2;9.2 OSA and Cognition;194
1.7.2.1.3;9.3 Cognitive and Behavioral Effects of IH;195
1.7.2.1.4;9.4 Pathophysiology of IH-Induced Cognitive Deficits;198
1.7.2.1.5;9.5 Environmental and Lifestyle Modulation of End-Organ Susceptibility;203
1.7.2.1.6;9.6 Effects of Sustained and Intermittent Hypoxia on Respiratory Control;204
1.7.2.1.6.1;9.6.1 Sustained Hypoxia and Control of Breathing;204
1.7.2.1.6.2;9.6.2 Effects of Intermittent Hypoxia on Respiratory Control;205
1.7.2.1.7;9.7 Effects of Acute Intermittent Hypoxia on Respiratory Plasticity;206
1.7.2.1.8;9.8 Effects of Chronic Intermittent Hypoxia on Respiratory Plasticity;208
1.7.2.1.9;9.9 Summary;209
1.7.2.1.10;References;210
1.7.3;Chapter 10;219
1.7.3.1;Brainstem Sensitivity to Hypoxia and Ischemia;219
1.7.3.1.1;10.1 Introduction;219
1.7.3.1.2;10.2 The Acute Response to Hypoxia;220
1.7.3.1.2.1;10.2.1 Cerebral Vasodilation and Blood Flow;220
1.7.3.1.2.2;10.2.2 Brain Stem;221
1.7.3.1.3;10.3 Global Ischemia;223
1.7.3.1.4;10.4 Chronic Hypoxia;223
1.7.3.1.4.1;10.4.1 Adaptation to Prolonged Mild Hypoxia;223
1.7.3.1.4.2;10.4.2 The Ventilatory Response;223
1.7.3.1.4.3;10.4.3 Cerebral Blood Flow;224
1.7.3.1.4.4;10.4.4 Angiogenesis;226
1.7.3.1.5;10.5 Conclusions;227
1.7.3.1.6;References;228
1.7.4;Chapter 11;230
1.7.4.1;Matrix Metalloproteinases in Cerebral Hypoxia-Ischemia;230
1.7.4.1.1;11.1 Introduction;231
1.7.4.1.2;11.2 Crystal Structure Model of S-Nitrosylation of MMPs;232
1.7.4.1.3;11.3 Neuronal NOS-Associated Activation of MMP During Cerebral Hypoxia/Ischemia;233
1.7.4.1.4;11.4 S-Nitrosylation of Recombinant MMP Leads to Its Activation;234
1.7.4.1.5;11.5 MMP Proteolysis-Mediated Neuronal Apoptosis in Cerebrocortical Cultures;235
1.7.4.1.6;11.6 Oxidative Modification Following S-Nitrosylation of MMP In Vitro and In Vivo;236
1.7.4.1.7;11.7 Increased MMP Gelatinolytic Activity Spatially Associated with Neuronal Laminin in the Ischemic Brain;238
1.7.4.1.8;11.8 Inhibition of MMP Proteolysis Prevents Laminin Degradation and Rescues Neurons from Ischemia;238
1.7.4.1.9;11.9 Summary;240
1.7.4.1.10;References;241
1.7.5;Chapter 12;244
1.7.5.1;Oxidative Stress in Hypoxic-Ischemic Brain Injury;244
1.7.5.1.1;12.1 Reactive Oxygen Species: Overview;244
1.7.5.1.2;12.2 Sources of ROS in Hypoxia-Ischemia;247
1.7.5.1.2.1;12.2.1 Mitochondria;247
1.7.5.1.2.2;12.2.2 The NADPH Oxidase (Nox) Family of Superoxide-Generating Enzymes in Hypoxia-Ischemia;249
1.7.5.1.2.3;12.2.3 Nitric Oxide Synthase (NOS);251
1.7.5.1.2.4;12.2.4 Other Sources of ROS;252
1.7.5.1.3;12.3 Effects of ROS on Blood–Brain Barrier Integrity and Cerebral Microvasculature;253
1.7.5.1.4;12.4 Effects of ROS on Neuronal Circuits and Synaptic Function in Hypoxia-Ischemia;254
1.7.5.1.5;12.5 Antioxidant Strategies to Test the Contribution of ROS to CNS Alterations and Injury After HI;255
1.7.5.1.6;12.6 Summary;255
1.7.5.1.7;References;255
1.7.6;Chapter 13;260
1.7.6.1;Postnatal Hypoxia and the Developing Brain: Cellular and Molecular Mechanisms of Injury;260
1.7.6.1.1;13.1 Introduction;260
1.7.6.1.2;13.2 Normal Brain Development;261
1.7.6.1.3;13.3 Altered Brain Development During Hypoxia;262
1.7.6.1.4;13.4 Hypoxia and the Stage of Development;262
1.7.6.1.5;13.5 Neurocognitive Effects of Postnatal Hypoxia;263
1.7.6.1.6;13.6 Hypoxia and Altitude: Lessons from Life at High Altitude;263
1.7.6.1.7;13.7 Cellular and Molecular Mechanisms of Hypoxic Cell Injury and Death;264
1.7.6.1.7.1;13.7.1 Cell Type-Specific Responses;265
1.7.6.1.7.2;13.7.2 Brain Region-Specific Responses;265
1.7.6.1.7.3;13.7.3 Ion Channel and Transporter Mechanisms;266
1.7.6.1.7.4;13.7.4 Hypoxia and Metabolic Arrest;266
1.7.6.1.7.5;13.7.5 Hypoxia and Apoptosis: Glutamate Excitotoxicity;267
1.7.6.1.7.6;13.7.6 Hypoxia and ROS;268
1.7.6.1.7.7;13.7.7 Hypoxia and the Immune System;270
1.7.6.1.7.8;13.7.8 Hypoxia and Gene Transcription;271
1.7.6.1.8;13.8 Summary;273
1.7.6.1.9;References;273
1.7.7;Chapter 14;282
1.7.7.1;Hypoxia-Inducible Factor 1;282
1.7.7.1.1;14.1 Oxygen Homeostasis and Its Impact on Evolution, Development, and Disease;282
1.7.7.1.2;14.2 Molecular Mechanisms of Oxygen Sensing;283
1.7.7.1.3;14.3 Regulation of Erythropoietin Production by HIF-1;285
1.7.7.1.4;14.4 Regulation of Angiogenesis by HIF-1;285
1.7.7.1.5;14.5 HIF-1 Is Required for Carotid Body-Mediated Responses to Continuous Hypoxia;286
1.7.7.1.6;14.6 HIF-1 Is Required for Carotid Body-Mediated Responses to Intermittent Hypoxia;287
1.7.7.1.7;14.7 Role of HIF-1 In Cerebral Preconditioning Phenomena;288
1.7.7.1.8;References;289
1.7.8;Chapter 15;294
1.7.8.1;Transcriptional Response to Hypoxia in Developing Brain;294
1.7.8.1.1;15.1 Introduction;294
1.7.8.1.2;15.2 Hypoxia-Responsive Transcription Factors in the Brain;295
1.7.8.1.3;15.3 Transcriptional Response to Hypoxia in Developing Brain;298
1.7.8.1.4;15.4 Summary;306
1.7.8.1.5;References;306
1.7.9;Chapter 16;312
1.7.9.1;Acute Stroke Therapy: Highlighting the Ischemic Penumbra;312
1.7.9.1.1;16.1 Introduction;312
1.7.9.1.2;16.2 The Concept of Ischemic Penumbra;313
1.7.9.1.3;16.3 The Existence and the Evolution of Ischemic Penumbra;314
1.7.9.1.4;16.4 Possible Mechanisms of the Penumbral Cell Death;316
1.7.9.1.4.1;16.4.1 Cell Death in the Infarct Core;317
1.7.9.1.4.2;16.4.2 Challenges of Penumbral Cells by Direct Exposure to the Core Milieu;317
1.7.9.1.4.2.1;16.4.2.1 Acidosis;317
1.7.9.1.4.2.2;16.4.2.2 Ionic Disturbances;318
1.7.9.1.4.2.3;16.4.2.3 Glutamate Toxicity;322
1.7.9.1.5;16.5 Penumbra and the Acute Stroke Therapy;322
1.7.9.1.6;16.6 Conclusion;324
1.7.9.1.7;References;324
1.7.10;Chapter 17;328
1.7.10.1;Genes and Survival to Low O2 Environment: Potential Insights from Drosophila;328
1.7.10.1.1;17.1 Introduction: Why Flies?;328
1.7.10.1.2;17.2 Strategies for Understanding Hypoxic Injury in the CNS;329
1.7.10.1.3;17.3 Our Specific Focus: Insights from Microarray Analysis;329
1.7.10.1.4;17.4 Role of Single Genes in an Inherited Complex Trait;331
1.7.10.1.5;17.5 Is Hypoxia Survival Related to Various Genetic Pathways?;333
1.7.10.1.6;17.6 Single Gene Vs. Multigenic Diseases;334
1.7.10.1.7;17.7 Fly Genes and Relevance to Mammalian Hypoxic Brain Injury;335
1.7.10.1.8;17.8 Summary;336
1.7.10.1.9;References;337
1.8;Index;339
1.9;Color Plates;348
