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It is well known and researched, that deprivation of oxygen to the brain can quickly result in irreversible damage and death. What is less well known, is that some vertebrate species are exceptionally tolerant of brain hypoxia. The Brain Without Oxygen: Causes of failure - Physiological and molecular mechanisms for survival, Third edition, discusses the mechanisms of brain hypoxia tolerance in these exceptional vertebrates, which include diving marine mammals, high altitude dwellers and the hibernating mammal. Special attention is given to the extraordinary adaptations that allow a few turtle and fish species to tolerate months of brain anoxia.

This third, fully updated edition addresses the potential of these animal models as targets for human clinical intervention. Perhaps the most interesting of these, are those involved in the suppression of metabolic activities to new set points well below their normoxic minima or maintenance levels. This volume will be valuable reading for researchers in physiology, medicine and general biological sciences, and of great importance to pharmaceutical companies researching novel models for stroke and brain ischemia.

The Brain Without Oxygen: Causes of Failure. Physiological and Molecular Mechanisms for Survival

1. Introduction.2. Normal Brain Function. Neuronal Communication. Brain Energy Consumption.3. Oxygen Sensing and Hypoxia Signaling. Introduction. Theories of Oxygen Sensing. Hypoxia Signaling in the Brain. Mechanisms of Transcriptional Activation by HIF-1. Hypoxia Responsive Genes and Neuroprotection. Hypoxia Response Pathways that do not Involve HIF-1. Oxygen Sensing Ion Channels. Summary.4. The Brain in Crisis. Introduction. Energy Failure. Phase 1: Metabolic Depression, a Mechanism for Protection. Phase 2: Complete Energy Failure and Anoxic Depolarization. Phase 3: Neuronal Destruction. Nitric Oxide Production. Free Radical Formation. Lipolysis. Cell Swelling. Lactate and Acidosis. Mitochondrial Damage. Apoptosis. Conclusions.5. Molecular Aspects of Brain Ischemia in Mammals. Introduction. In Vivo Models of Cerebral Ischemia. Molecular Signaling Pathways Regulating Death and Survival in Cerebral Ischemia. Gene Activation and Transcription Factor Induction in Cerebral Ischemia. Activation of Heat Shock Protein Genes. Signaling Molecules in Cerebral Ischemia. Mediators and Modulators of Apoptosis. Summary.6. Brains that survive: Adaptations to Anoxia. Introduction. Phylogenetic Factors. Transition to the Anoxic State. The Anoxic State.7. Mechanisms of Brain Anoxia Tolerance. Introduction. Energy Production. Metabolic Depression. Electrical Activity. Neurotransmitters and Neuromodulators. Ion Channels. pH and CO2. Free Radicals. Protein Synthesis. Brain Swelling. Freshwater Turtles Versus Carassius. Conclusions.8. Special Cases of enhanced Tolerance. The Mammalian Neonate. The Hibernating Mammal. The Marine Mammal. High Altitude Hypoxia. The Tidal Shark. The Anoxic Frog.9. Acclimation to Hypoxia in Mammals: Preconditioning. Ischemic Preconditioning. Early and Late Myocardial Preconditioning. Adenosine Receptors. KATP Channels. Nitric Oxide and Reactive Oxygen Species. Protein Kinase C and Other Signaling Kinases. Ischemic Preconditioning in the Brain. Summary.10. Clinical Perspectives. Anoxic Depolarization Delayed. Protection from Consequences of Anoxic Depolarization. Novel Molecular Targets and Hypoxia Regulated Gene Therapy.Index.