Brain Ischemia

Ischemia is localized tissue anemia due to obstruction of the inflow of arterial blood, thus brain ischemia is the condition where insufficient blood is delivered to the brain. Many physiological processes occurring in the brain critically depend on the state of its energy metabolism. The state of brain energy metabolism in turn depends on the delivery of oxygen and glucose to the brain via the bloodstream. Although it comprises only 2% of the total body weight, the human brain consumes 20-25% of the oxygen and up to 70% of the free glucose taken in by the body. The brain respires more intensively than any other organ of the body. The intensity of oxygen consumption by cortical brain tissue much exceeds the demands of other tissues (5.43 mmol 02/g per h versus 3.06 and 4.02 mmol for heart at rest and intensively working, respectively, 2.4 mmol for kidneys, and 1.8 mmol for liver). Oxidative phosphorylation in mitochondria generates 95% of the adenosine triphosphate (ATP) that is formed in the brain. Thus, it is clear why insufficiency of oxygen delivery to brain cells adversely affects brain function. Glucose is the main energy-providing substrate in the brain. The basic pathway of its metabolism in neural tissue is aerobic glycolysis. Front Matter....Pages i-xiv Introduction....Pages 1-5 Front Matter....Pages 7-7 Hemodynamic Events Associated with Acute Focal Brain Ischemia and Reperfusion. Ischemic Penumbra....Pages 9-19 Cellular Reactions in Response to Acute Focal Brain Ischemia....Pages 21-29 Energy Failure Induced by Brain Ischemia....Pages 31-37 The Glutamate—Calcium Cascade....Pages 39-93 Metabolic Acidosis and Ischemic Damage....Pages 95-99 Delayed Neuronal Death Following Acute Focal Brain Ischemia....Pages 101-102 Gene Expression and Subsequent Molecular Events in Response to Acute Brain Ischemia....Pages 103-114 Microglial Activation, Cytokine Production, and Local Inflammation in Focal Brain Ischemia....Pages 115-145 Autoimmune Mechanisms of Trophic Dysfunction and Ischemic Brain Damage....Pages 147-182 Programmed Cell Death. Apoptosis in Focal Brain Ischemia....Pages 183-205 Reaction of the Stress-Mediating Endocrine System in Response to Acute Brain Ischemia....Pages 207-217 Molecular Mechanisms of Post-Ischemic Reparation Events....Pages 219-226 Front Matter....Pages 227-227 Modern Therapeutic Approaches to Acute Focal Brain Ischemia. Basic Strategies for Neuroprotection....Pages 229-236 Primary Neuroprotection....Pages 237-284 Secondary Neuroprotection....Pages 285-351 Reparative Therapy....Pages 353-368 Strategies and Prospects for Development of Neuroprotective Therapy for Brain Ischemia....Pages 369-376 Conclusion....Pages 377-378 Back Matter....Pages 379-392 This monograph highlights modern concepts of brain ischemia and strategies of neuroprotective therapy. The first part of the book is devoted to mechanisms of ischemic brain damage. The authors present the results of their own clinical and experimental studies conducted in the last two decades, as well as the achievements of native and foreign neurological researches that open a new stage in understanding how reversible changes of blood flow and metabolism are transformed into a permanent morphological lesion, i.e. brain infarction. The most important advances in areas of ischemic energy failure, main mechanisms of the glutamate-calcium cascade, influence of metabolic acidosis on ischemic damage, delayed neuronal death connected with microglial activation, local inflammation, autoimmune reactions, trophic dysfunction, and apoptosis, as well as of reaction of the stress-mediating endocrine system to focal brain ischemia are shown in animals and humans, and the relevant literature is cited and critiqued. The book also explores topics that recently have experienced substantial growth, such as gene expression and subsequent molecular events in response to acute brain ischemia, connected with both tissue damage and reparation. The authors demonstrate not only universal features of the process of brain ischemia, but also individual peculiarities of its course in patients and analyse their reasons Introduction. Part I: Mechanisms of Ischemic Brain Damage. 1. Hemodynamic Events Associated with Acute Focal Brain Ischemia and Reperfusion. Ischemic Penumbra. 2. Cellular Reactions in Response to Acute Focal Brain Ischemia. 3. Energy Failure Induced by Brain Ischemia. 4. The Glutamate-Calcium Cascade. 4.1. The Induction Stage: Energy-Dependent Ion Pump Failure And Glutamate Excitotoxicity. 4.2. The amplification stage: intracellular accumulation of calcium ions, spreading glutamate release, spreading depression waves. 4.3. The expression stage: calcium-inducedactivation of intracellular enzym