The Brain Without Oxygen

by Lutz, Peter L.; Nilsson, G. E.; Nilsson, Goran E.; Prentice, Howard M.

• ISBN13: 9781402011658
• ISBN10: 1402011652
• Edition: 3rd
• Format: Hardcover
• Copyright: 2003-05-01
• Publisher: Kluwer Academic Pub

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