Brain Ischemia

A distinction between primary and secondary brain damage of vari ous origin, particularly in acute lesions, such as head injury and ische mia is not entirely new. The concept is of practical significance, be cause it is the foremost intention of all clinical efforts to prevent, or at least attenuate the development of secondary sequelae. Primary dam age to nervous elements usually cannot be influenced by treatment. Its prevention is the objective of prophylactic measures. The current volume gathered prominent scientists and clinicians from various fields to pro vide a competent introduction and survey of the various aspects involved in secondary brain damage. It was attempted to provide criteria for the distinction between the primary and secondary phenomena on a morpho logical and functional level, on the basis of the kinetics involved and, most importantly, regarding the different specific manifestations, such as disturbances of microcirculation, aspects of the blood-brain barrier, and of cellular structure and function at a molecular level. Although it was not expected that a grand unifying hypothesis will be reached recon cilable with the many, occasionally opposing views on such a complex subject, nevertheless, the present volume attains an appropriate result. It can best be described as a mosaic of many different pieces which only as an ensemble reflect the current state of the art.

The human brain represents about 2% of the body weight, yet it accounts for approximately 20% of aerobic metabolism. This high dependency on energy-consuming processes is mainly caused by the active transport of ions, which is necessary to compensate for the transmembrane ion currents that are part ofthe complex signaling processes in the brain. Ninety-five percent ofthe brain's ATP is derived from mitochondrial oxidative phosphorylation. Since that organ' s storage capacity for oxygen is minimal, any interruption of oxygen delivery to brain cells willlead to changes in membrane excitability and, there fore, to disruption of neuronal signaling within seconds. It seems that mamma lian brain is especially vulnerable to such an interruption, since oxygen deprivation leads to activation of ion channel mechanisms in neurons that impair their communications. Thus, the function of the brain as a coordinator of vital homeostatic reflexes, and complex body reactions to external challenges, depends critically on the rate of oxygen delivery and oxygen consumption. Oxygen delivery depends on two variables described in the Fick relation ship: volume flow rate ofblood and the arterial oxygen content. A reduction in either of these two variables will have serious effects on vital brain func tions. Reduction of arterial blood flow to the brain can be caused by cardiac arrest, shock, carotid occlusion, Of hypotension (global ischemia). Oxygen content is progressively decreased in asphyxia (including drowning).

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.

Professor Caplan has extensively edited the book to shape and organize the contents into a succinct presentation by experts of the basic science and clinical aspects of the topic. The text has been divided into sections: The Brain.- Macroscopic and microscopic molecular aspects of brain ischemia, including pathophysiology, pathology, biochemistry, and clinical measurement.- Blood Vessels.- Their constitution and the pathology and physiology of the endothelium and arterial wall.- Blood Flow.- Its physics, control, rheology, and pathophysiology.- Blood.- The role of the cellular and serological constituents in coagulation and fibrinolysis. - Heart.- Sources of embolism and cardiac changes caused by brain ischemia.- And Epidemiology, Databases, and Trials. Prefatory remarks by Professor Caplan introduce each section. At the end of each section he relates the basic concepts to patient problems in the clinic, integrates the various contributions in the section, and covers other areas not discussed by the individual contributors.

Brain Hypoxia and Ischemia 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 O2 levels are dysregulated. Brain Hypoxia and Ischemia is designed for neuroscientists, clinicians and medical/graduate students for use in both basic research and clinical practice.

This updated second edition of Acute Ischemic Stroke: Imaging and Intervention provides a comprehensive account of the state of the art in the diagnosis and treatment of acute ischemic stroke. The basic format of the first edition has been retained, with sections on fundamentals such as pathophysiology and causes, imaging techniques and interventions. However, each chapter has been revised to reflect the important recent progress in advanced neuroimaging and the use of interventional tools. In addition, a new chapter is included on the classification instruments for ischemic stroke and their use in predicting outcomes and therapeutic triage. All of the authors are internationally recognized experts and members of the interdisciplinary stroke team at the Massachusetts General Hospital and Harvard Medical School. The text is supported by numerous informative illustrations, and ease of reference is ensured through the inclusion of suitable tables. This book will serve as a unique source of up-to-date information for neurologists, emergency physicians, radiologists and other health care providers who care for the patient with acute ischemic stroke.

Cerebral Blood Flow: Quantifying Consciousness Although the heart may be the source of energy needed to generate blood flow,and other organs absolutely essential for normal living,the brain is the reason we are alive. The collected book chapters are aimed at addressing this most fundamental organ and its blood flow. These papers reflect detailed descriptions of similar topics presented over a two-day period as part of the 5th International Symposium on Applied Physiology of the Peripheral Circulation held in Pittsburgh, Pennsylvania, in June 2000. The symposium and this volume were organized into four distinct groupings that follow in a logical fashion. The initial papers focus on the basic unique physiology and pathophysiology of the cerebral circulation, including a historical reviewof the means to measure cerebral blood flow and its implications of the past 30 years. Dr. Walter D. Obrist was one of the original investigators to use radiolabeled markers to assess cerebral blood flow. His equations and initial studies form an impressive introduction to where we are now. As with much of the body's special organs, the brain too has many circulatory features unique to itself.These include the unique blood-brain barrier function ofthe endothelium, local neural regulation control, and intracranial pressure effects. These special issues,plus genetic factors that may predispose individuals to developing cere bral aneurysm, make up the initial section of the monograph.

Approximately half a million Americans suffer brain ischemic episodes every year. These brain strokes are the third leading cause of death in the United States and the number-one cause of permanent disability. Over the past decade, we have made extensive attempts to understand the biological mechanisms that underlie stroke-induced neuronal injury.