Cerebral Ischemia And Basic Mechanisms

In this volume, one of a series of monographs devoted to the problems of cerebral ischemia and related topics, we present the proceedings of an international conference on Cerebral Ischemia and Basic Mechanisms held in Bad Schachen/Lake Constance, Germany in June 1992. The enormous progress in research recently on the basic mechanisms associated with cerebral ischemia has provided greater insight into the pathophysiological mechanisms of reduced brain perfusion and decreased cerebral metabolism. The high technology instrumentation used to unravel the intricacies of cerebral blood flow and metabolism includes positron emission tomography and magnetic resonance imaging. A description of sophisticated neurophysiological techniques will give the reader insight into new models of reversible and irreversible tissue damage and changes at the molecular level have been described. The therapeutic approaches which have developed from this re search have been or will be used in clinical trials and will open new avenues in the treatment of stroke. The organizers of the meeting would like to thank the advisory board for its helpful suggestions and the Deutsche Forschungsgemeinschaft and other sponsors for their important support.

'... Provides an admirable review of current knowledge regarding experimental stroke research, and outlines the problems and some solutions in the clinical application of such knowledge.'

A compilation of innovative findings and new directions in neurological recovery After decades of focusing on how to alleviate and prevent recurrence of acute CNS injuries, the emphasis has finally shifted towards repairing such devastating events and rehabilitation. This development has been made possible by substantial progress in understanding the scientific underpinnings of recovery as well as by novel diagnostic tools, and most importantly, by emerging therapies awaiting clinical trials. In this publication, several international experts introduce novel areas of neurological reorganization and repair following CNS damage. Principles and methods to monitor and augment neuroplasticity are explored in depth and supplemented by a critical appraisal of neurological repair mechanisms and possibilities to curtail disability using computer or robotic interfaces. Rather than providing a textbook approach of CNS restoration, the editors selected topics where progress is most imminent in this labyrinthine domain of medicine. Moreover, the varied background and origins of the contributors lend this book a truly global perspective on the current state of affairs in neurological recovery.

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.

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.

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.

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).

The publication of the Vth International Symposium 1995 on "Mechanisms of Secondary Brain Damage" in Mauls/ltaly is a collection of focused reviews reaching from novel molecular- and cell biological findings to aspects of clinical management in head injury and cerebral ischemia. A specific purpose of these series of meetings introduced in 1984 is for an exchange on problems of mutual interest by international high ranking experts from the basic sciences and related clinical disciplines, such as intensive care medicine, neurology, or neurosurgery. The present volume covers three major areas: (a) Molecular and cell biological mechanisms including inflammation (b) Novel findings on mechanisms and treatment in cerebral ischemia (c) Secondary processes in head injury, regeneration and treatment Molecular-and cell biology is currently attracting attention towards activation of genomic processes associated with the demise of cells referred to as "programmed cell death" and "apoptosis" which, actually, might be distinguished from each other. Thus, the phenomenon of delayed neuronal death in selectively vulnerable brain areas following brief interruption of blood flow is scrutinized as to the contribution of the activation of suicide genes. The physiological role of such a response, among others, is removal of surplus neurons during ontogenesis of the brain. Yet, evidence is accumulating that similar mechanisms playa role in cerebral ischemia, probably also trauma, where nerve-and other cells demonstrate features of apoptosis. Observations on protection of neurons by administration of protein synthesis inhibitors in cerebral ischemia provide more direct support.