The Brain Without Oxygen

by ; ; ;
Edition: 3rd
Format: Hardcover
Pub. Date: 2003-05-01
Publisher(s): Kluwer Academic Pub
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Summary

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.

Table of Contents

1. Introduction 1(2)
2. Normal Brain Function 3 (40)
Neuronal Communication
3 (26)
Brain Energy Consumption
29(14)
3. Oxygen Sensing and Hypoxia Signaling 43(18)
Introduction
43(1)
Theories of Oxygen sensing
44(3)
Hypoxia Signaling in the Brain
47 (2)
Mechanisms of Transcriptional Activation by HIF-1
49 (2)
Hypoxia Responsive Genes and Neuroprotection
51 (1)
Hypoxia Response Pathways that do not Involve HIF-1
52 (1)
Oxygen Sensing Ion Channels
53 (1)
Summary
54(7)
4. The Brain in Crisis 61 (42)
Introduction
61 (1)
Energy Failure
62 (4)
Phase 1: Metabolic Depression, a Mechanism for Protection
66 (2)
Phase 2: Complete Energy Failure and Anoxic Depolarization
68 (9)
Phase 3: Neuronal Destruction
77 (5)
Nitric Oxide Production
82 (5)
Free Radical Formation
87 (3)
Lipolysis
90(1)
Cell swelling
91(1)
Lactate and Acidosis
91 (2)
Mitochondrial Damage
93 (1)
Apoptosis
94 (1)
Conclusions
94(9)
5. Molecular Aspects of Brain Ischemia in Mammals 103 (16)
Introduction
103 (1)
In Vivo Models of Cerebral Ischemia
104 (1)
Molecular Signaling Pathways Regulating Death and Survival in Cerebral Ischemia
104 (1)
Gene Activation and Transcription Factor Induction in Cerebral Ischemia
105 (1)
Activation of Heat Shock Protein Genes
106 (1)
Signaling Molecules in Cerebral Ischemic
107 (3)
Mediators and Modulators of Apoptosis
110 (5)
Summary
115(4)
6. Brains that survive: Adaptations to Anoxia 119 (12)
Introduction
119 (1)
Phylogenetic Factors
120 (2)
Transition to the Anoxic state
122 (2)
The Anoxic State
124(7)
7. Mechanisms of Brain Anoxia Tolerance 131 (60)
Introduction
131 (1)
Energy Production
132 (10)
Metabolic Depression
142 (2)
Electrical Activity
144 (4)
Neurotransmitters and Neuromodulators
148 (14)
Ion Channels
162 (8)
pH and CO2
170 (2)
Free Radicals
172 (2)
Protein Synthesis
174 (1)
Brain Swelling
175 (1)
Freshwater Turtles Versus Carassius
176 (4)
Conclusions
180(11)
8. Special Cases of enhanced Tolerance 191 (24)
The Mammalian Neonate
191 (5)
The Hibernating Mammal
196 (4)
The Marine Mammal
200 (3)
High Altitude Hypoxia
203 (2)
The Tidal Shark
205 (1)
The Anoxic Frog
206(9)
9. Acclimation to Hypoxia in Mammals: Preconditioning 215 (16)
Ischemic Preconditioning
215 (1)
Early and Late Myocardial Preconditioning
216 (1)
Adenosine Receptors
216(1)
KATP Channels
217(2)
Nitric Oxide and Reactive Oxygen Species
219 (1)
Protein Kinase C and Other Signaling Kinases
219 (2)
Ischemic Preconditioning in the Brain
221 (4)
Summary
225(6)
10. Clinical Perspectives 231 (18)
Anoxic Depolarization Delayed
232 (8)
Protection from Consequences of Anoxic Depolarization
240 (1)
Novel Molecular Targets and Hypoxia Regulated Gene Therapy
241(8)
Index 249

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