Hepatic Encephalopathy (HE) is a neuropsychiatric disorder resul t- ing from liver failure. HE may be associated with fulminant (acute) hepatic failure or chronic liver disease with portal-systemic shunting. The latter condition is characterized neuropathologically by astro- cytic rather than neuronal changes (Alzheimer Type II astrocytosis). The former is frequently accompanied by cerebral edema. Several hypotheses have been proposed to explain the pathogene- sis of HE. These include: 1. A toxic action of a substance (or substances) such as ammonia on brain function 2. A deficit of cerebral energy metabolism 3. Neurotransmitter changes, and, more recently 4. The role of "endogenous benzodiazepines. " This volume summarizes the results of a symposium held in Val David, Quebec from October 3D-November I, 1988, that was devoted to an evaluation of the evidence for and against the various hypothe- ses of HE. Data from studies in patients, in experimental (animal) models of HE, and in cultured cell preparations were discussed. In addition, a review of available approaches to the treatment and man- agement of HE was included. The therapeutic use of lactulose, anti- biotics, dietary treatment, and branched-chain amino acid treatments were included, as well as the results of preliminary studies of the therapeutic use of the benzodiazepine antagonist, flumazenil. Roger F. Butterworth, PhD Gilles Pomier Layrargues, MD v Acknowledgments The symposium was made possible by the generous financial assistance of: Hoffman-La Roche Ltd.

to the Animal Models Volumes This and several other volumes in the Neuromethods series will describe a number of animal models of neuropsychiatric disorders. Because of increasing public concern over the ethical treatment of animals in research, we felt it incumbent upon us to include this general preface to these volumes in order to indicate why we think further - search using animals is necessary and why animal models of psychiatric disorders, in particular, are so important. We recognize that animals should only be used when suitable alternatives are not available. We think it self-e- dent, however, that humans can only be experimented upon in severely proscribed circumstances and alternative pro- dures using cell or tissue culture are inadequate in any models requiring assessments of behavioral change or of complex in vivo processes. However, when the distress, discomfort, or pain to the animals outweighs the anticipated gains for human welfare, then the research is not ethical and should not be carried out. It is imperative that each individual researcher examine his/her own research from a critical moral standpoint - fore engaging in it, taking into consideration the animals' welfare as well as the anticipated gains. Furthermore, once a decision to proceed with research is made, it is the researcher's responsibility to ensure that the animals' w- fare is of prime concern in terms of appropriate housing, feeding, and maximum reduction of any uncomfortable or distressing effects of the experimental conditions, and that these conditions undergo frequent formalized monitoring.

to the Animal Models Volumes This and several other volumes in the Neuromethods series will describe a number of animal models of neu- psychiatric disorders. Because of increasing public concern over the ethical treatment of animals in research, we felt it incumbent upon us to include this general preface to these volumes in order to indicate why we think further research using animals is necessary and why animal models of psychi- ric and neurologic disorders, in particular, are so important. We recognize that animals should only be used when suitable alternatives are not available. We think it self-e- dent, however, that humans can only be experimented upon in severely proscribed circumstances and alternative pro- dures using cell or tissue culture are inadequate in any models requiring assessments of behavioral change or of complex in vivo processes. However, when the distress, discomfort, or pain to the animals outweighs the anticipated gains for human welfare, then the research is not ethical and should not be carried out.

to the Animal Models Volumes This and several other volumes in the Neuromethods series will describe a number of animal models of neu- psychiatric disorders. Because of increasing public concern over the ethical treatment of animals in research, we felt it incumbent upon us to include this general preface to these volumes in order to indicate why we think further research using animals is necessary and why animal models of psychi- ric and neurologic disorders, in particular, are so important. We recognize that animals should only be used when suitable alternatives are not available. We think it self-e- dent, however, that humans can only be experimented upon in severely proscribed circumstances and alternative pro- dures using cell or tissue culture are inadequate in any models requiring assessments of behavioral change or of complex in vivo processes. However, when the distress, discomfort, or pain to the animals outweighs the anticipated gains for human welfare, then the research is not ethical and should not be carried out.

to the Animal Models Volumes This and several other volumes in the Neuromethods series will describe a number of animal models of neuropsychiatric disorders. Because of increasing public concern over the ethical treatment of animals in research, we felt it incumbent upon us to include this general preface to these volumes in order to indicate why we think further - search using animals is necessary and why animal models of psychiatric disorders, in particular, are so important. We recognize that animals should only be used when suitable alternatives are not available. We think it self-e- dent, however, that humans can only be experimented upon in severely proscribed circumstances and alternative pro- dures using cell or tissue culture are inadequate in any models requiring assessments of behavioral change or of complex in vivo processes. However, when the distress, discomfort, or pain to the animals outweighs the anticipated gains for human welfare, then the research is not ethical and should not be carried out. It is imperative that each individual researcher examine his/her own research from a critical moral standpoint - fore engaging in it, taking into consideration the animals' welfare as well as the anticipated gains. Furthermore, once a decision to proceed with research is made, it is the researcher's responsibility to ensure that the animals' w- fare is of prime concern in terms of appropriate housing, feeding, and maximum reduction of any uncomfortable or distressing effects of the experimental conditions, and that these conditions undergo frequent formalized monitoring.

Hepatic Encephalopathy (HE) is a neuropsychiatric disorder resul t- ing from liver failure. HE may be associated with fulminant (acute) hepatic failure or chronic liver disease with portal-systemic shunting. The latter condition is characterized neuropathologically by astro- cytic rather than neuronal changes (Alzheimer Type II astrocytosis). The former is frequently accompanied by cerebral edema. Several hypotheses have been proposed to explain the pathogene- sis of HE. These include: 1. A toxic action of a substance (or substances) such as ammonia on brain function 2. A deficit of cerebral energy metabolism 3. Neurotransmitter changes, and, more recently 4. The role of "endogenous benzodiazepines. " This volume summarizes the results of a symposium held in Val David, Quebec from October 3D-November I, 1988, that was devoted to an evaluation of the evidence for and against the various hypothe- ses of HE. Data from studies in patients, in experimental (animal) models of HE, and in cultured cell preparations were discussed. In addition, a review of available approaches to the treatment and man- agement of HE was included. The therapeutic use of lactulose, anti- biotics, dietary treatment, and branched-chain amino acid treatments were included, as well as the results of preliminary studies of the therapeutic use of the benzodiazepine antagonist, flumazenil. Roger F. Butterworth, PhD Gilles Pomier Layrargues, MD v Acknowledgments The symposium was made possible by the generous financial assistance of: Hoffman-La Roche Ltd.