This fascinating monograph is filled with information formerly found only in periodicals and symposia proceedings. Chapters discuss the different models of cerebral ischemia in use today, including their advantages and disadvantages. This one-of-a-kind resource also contains essential chapters on cellular mechanisms of ion and acid-base homeostases, and energy metabolism of the ischemic brain. It reviews the possible role of lipids, free fatty acids, and free radicals. Four chapters are devoted to neurotransmitters and neuroregulators in cerebral ischemia. This extraordinary work also covers aspects of protection against and resuscitation from cerebral ischemia. An extremely informative volume, this book is an absolute must for every student in the field of cerebral ischemia, as well as the clinician or scientist who is already involved with this worldwide problem.

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.

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 Maturation Phenomenon, described by Ito et al. in 1975 [3) on the basis of his to logical observations in the hippocampus as well as other portions of the cerebral hemisphere, refers to the hours or days of delay in the development of pathological changes in various parameters of ischemic injury following the restoration of blood flow to the ischemic brain. There is a direct relationship between the intensity of ischemic insult and the speed and rate of maturation of ischemic injury, a lesser intensity being associated with slower and less severe development of the lesions. The delayed neuronal death of CAl pyramidal cells of the hippocampus [8) is a classic example. In the cerebral cortex, with increasing intensity of the ischemic insult, the maturation phenomenon of ischemic injuries intensifies, seamlessly, from less exten sive to more extensive disseminated selective neuronal necrosis (DSNN), and then further to cerebral infarction upon reaching a critical threshold [1,2,4,6,7). We also have found that following ischemic insults just under the threshold level required to induce infarction, only disseminated selective neuronal necrosis (DSNN) progresses, while following ischemic insults at the threshold level, initially only DSNN develops, followed by the evolution of a gradually enlarging infarcted focus [5, 7). The reporting of this phenomenon boosted research in the field, as it became evi dent that ischemic damage is not a sudden event, but a process potentially susceptible to therapeutic intervention.

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.

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.

Although many books deal with isolated problems of calcium disturbance in relation to cardiac and cerebral function, this is the first to focus specifically on calcium metabolism and cerebral ischemia. Internationally acknowledged experts present recent data and new concepts in an interdisciplinary approach to the subject. They examine basic information on the pathophysiology of cellular events, the damage caused by excitotoxic substances, and the effects of calcium antagonistic drugs as measured in experimental animals. These contributions may help lead to possible therapeutic interference for the prevention of calcium imbalance.

A distinguished international panel of authors define our current understanding of neuronal damage after ischemia and critically review the significant recent developments and progress in cerebrovascular accident (CVA) drug trials, both in animal models and in the clinical setting. These leading basic and fundamental authorities survey such important new drugs as calcium-influx inhibitors, free-radical scavenging drugs, glutamate and glycinergic antagonists, and immune suppressors. They also evaluate all the latest findings concerning calcium homeostasis, glutamate toxicity, gene activation, and the role of free radicals, glycine, and hormones. Chapters devoted to the neuroimaging of stroke, clinical trials, and the role of cerebral immune activation complete this informative collection of cutting-edge reviews.