Brain Edema: From Molecular Mechanisms to Clinical Practice brings together the most widely recognized experts in experimental and clinical brain edema research to review the current knowledge gathered on the molecular and cellular pathophysiology and clinical management of brain edema. This timely book also discusses future directions of research and treatment. Brain edema is an integral and acutely life-threatening part of the pathophysiology of multiple cerebral and non-cerebral disorders, including traumatic brain injury, cerebral ischemia, brain tumors, cardiac arrest, altitude sickness and liver failure. Affecting millions worldwide, research over the past few years has shown that a plethora of complex molecular and cellular mechanisms contribute to this pathological accumulation of water in the brain parenchyma. In parallel, the development of new neuroimaging tools has provided a new way to examine how edema develops longitudinally and in real time, both in pre-clinical models and in patients. Despite intense research over the past few decades, therapeutic options are still limited and sometimes not effective. Presents a comprehensive understanding of the molecular mechanisms involved in edema formation and resolution Discusses the specific role of edema development in several pathologies, including traumatic brain injury, stroke, brain tumors, cardiac arrest, and liver failure Proposes a new classification of edema based on molecular processes Discusses clinical management of new clinical trials coming from pre-clinical studies Addresses the possible link between edema formation, other molecular and cellular processes, including inflammation and neuroinflammation

Brain edema is a simple phenomenon – an abnormal increase of brain tissue volume by the increase of brain tissue water content. However the etiology is not simple and relating to a wide variety of neurological disorders including ischemia, trauma, tumor, hemorrhage and hydrocephalus. It is still a major cause of death in the neurological/neurosurgical ward. This volume is an up-to-date report on progress in brain edema research, diagnosis and treatment, including papers presented at the 12th International Symposium on Brain Edema and Brain Tissue Injury in 2002. Major topics include molecular biology and blood-brain barrier disorders, ischemic and traumatic brain edema, imaging and diagnosis of brain edema, treatment and radiation effect. Various papers in the rapidly growing fields of neuroimaging and molecular medicine are also included.

The experimental brain edema as a result of application of numerous different toxic agents has been the subject of a large number of publications (for synopses see Hirano, 1969; Long et al. , 1965). A concept that took the underlying causes of the lesions as the basis for classification of different types of brain edema was presented by Klatzo (1967). In this classification Klatzo differentiates between cytogenic and vasogenic causes of brain edema that are distinguishable from each other by the differing behaviour and reaction of the blood-brain-barrier. The vasogenic type of brain edema is found mostly in the vicinity of tumors, traumata and foci of infections, presumably because of an alteration of the conditions of permeability, as well as in brain edemas that are caused by changes in the hemodynamics of the central nervous system, and toxic substances that act directly on the wall of the blood vessel. The cytogenic type of brain edema in many experimental models is the result of, for instance, TET-intoxication, water intoxication, poisoning with other chemical substances and anoxia. Its direct cause according to Klatzo (1967) is to be seen in a disturbance of the intra cellular osmoregulation of the parenchymal cells. Although the composition of the edema fluid is dependent on the type of toxic substance used, the lack of plasma proteins in the edema fluid is characteristic for the brain edemas of this group.

The control of brain edema is still one of the major problems in surgical and conservative treatment of various cerebral lesions. Many attempts have been made to develop methods for reducing the high mortality associated with brain edema. Mter many years of using hypertonic solutions it can be stated that this type of therapy has not yielded satisfactory results. During recent years increasing evidence has been accumulated on the efficacy of steroids on brain edema. Steroids were reported to result in rapid relief of signs and symptoms of increased intracranial pressure and neurological dysfunction accompanying cerebral edema. It was the aim of this workshop to evaluate the effect of corticosteroids on brain edema as an advance in therapy. It was hoped that this could be achieved by a multi disciplinary approach. Though, the volume contains the contributions of various experts - internists, neurochemists, neurologists, neuropathologists, neurosurgeons, pharmacologists, physiologists - who have added considerable experimental and clin ical evidence on the action of steroids on brain edema. New pathophysiological aspects regarding the mechanisms underlying the formation and resolution of brain The effectiveness of corticosteroid therapy in various forms edema are presented. of clinical and experimental brain edema, e. g. accompanying brain tumors, head injury, spinal cord injury, cerebrovascular lesions, etc. as well as dosage and duration of treatment are critically discussed.

The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

The Symposium on Brain Edema has been organized by the Osterreichische Arbeitsgemeinschaft fur Neuropathologie and by the Problem Commission for Neuropathology of the World Federa tion of Neurology. We would like to express our thanks to Dr. L. van Bogaert, president of the W.F.N., for his great interest in the design of this conference and for his energetic support. One of the aims ofthe Problem Commission for Neuropathology has been to contribute to the advances in various problems which are becoming ripe for elucidation by experts in different fields. The idea of the Symposium on Brain Edema has as its background a compelling necessity to elucidate this subject which is clinically so important and neuropathologic ally so poorly understood. It was hoped that this could be achieved by a multidisciplinary approach involving a variety of aspects to be discussed and correlated. Brain edema, being an abnormal cerebral condition, belongs basically to the sphere of neuropathology, but to be successful in our endeavors we had to apply neuropathology in its most modern and widest terms. By this we understand that such neuropathology includes the study of all abnormal phenomena in the nervous tissue related to the structural alterations, and by "structural" we mean not only tissual or cellular ones but also changes on ultrastructural and molecular levels. Thus we needed close and integrated coopera tion of experts in fields such as neurohistology, histochemistry, electron microscopy, neurochemistry, and neurophysiology.