Neuron-Glia Interrelations During Phylogeny I


Book Description

Leading international authorities report on their in vivo studies of neuron glia interactions in animals with simple nervous systems (insects, fish, amphibians, and reptiles). Their work amounts to an in-depth account of many of the principal functions of glial cells: myelination, regulation of ionic environment, neurotransmitter compartmentation and neurotransmitter receptors, blood brain barrier, regeneration, and aging. Part I examines the origin and role of glial cells during development across the phylogenetic spectrum, including the evolution of their particular functions. Part II discusses the physiological and metabolic interactions between neurons and glia, again across phylogenetic groups. Neuron Glia Interrelations During Phylogeny illuminates the evolution of the nervous system and expands our knowledge of the mechanisms involved in regeneration and central nervous system repair. It constitutes a virtual encyclopedia of up-to-date findings concerning the significant roles played by glial cells in neuronal development and function.




Neurotransmitter Transporters


Book Description

A comprehensive survey of recent advances made in characterizing neurotransmitter transporters-including their imaging in the living brain-and in elucidating the processes underlying biological transport. The expert contributors present up-to-date findings on the molecular cloning of transporters and on neurotransmitter families both in plasma membranes and in storage vesicles. They also provide essential information on the structure-activity relationships for a multitude of recently synthesized dopamine uptake blockers, on transporter changes in the context of human drug abuse, and on the role of transporters in the action of uptake blockers in vivo. The book opens the new frontier of transporters research, authoritatively presenting new insights into their roles in such diseases as brain ischemia and ALS, and into their involvement as targets for antidepressants, antiepileptics, drugs of abuse, and neurotoxins.




Gene Therapy for Neurological Disorders and Brain Tumors


Book Description

Leading gene therapy researchers and clinicians illuminate the field-from basic vector technology to current and future clinical applications in neurology. The authoritative contributors provide cutting-edge reviews of the vectors available for gene transfer to the central nervous system, the strategies against CNS tumors, the potential strategies against neurologic disorder, and the limitations of today's gene therapy approaches. Also discussed are significant applications of gene therapy to brain tumors, Parkinson's disease, ischemia, and Huntington's chorea. Readers will learn the current delivery methods for transgenes, will learn the characteristics of transgene delivery vectors, and come to understand the therapy for both neuro-oncologic and neurologic disorders.




Pathogenesis of Neurodegenerative Disorders


Book Description

As the average life expectancy of many populations throughout the world increases, so to does the incidence of such age-related neurodegenerative disorders as Alzheimer's, Parkinson's, and Huntington's diseases. Rapid advances in our understanding of the molecular genetics and environmental factors that either cause or increase risk for age-related neurodegenerative disor ders have been made in the past decade. The ability to evaluate, at the cellular and molecular level, abnormalities in postmortem brain tissue from patients, when taken together with the development of valuable animal and cell-culture models of neurodegenerative disorders has allowed the identification of sequences of events within neurons that result in their demise in specific neurodegenerative disorders. Though the genetic and environmental factors that pro mote neurodegeneration may differ among disorders, shared biochemical cascades that will ultimately lead to the death of neurons have been identified. These cascades involve oxyradical production, aberrant regulation of cellular ion homeostasis and activation of a stereotyped sequence of events involving mitochondrial dysfunction and activa tion of specific proteases. Pathogenesis of Neurodegenerative Disorders provides a timely compilation of articles that encompasses fundamental mechanisms involved in neurodegenerative disorders. In addition, mechanisms that may prevent age-related neurodegenerative disorders are presented. Each chapter is written by an expert in the particular neurodegenerative disorder or mechanism or neuronal death discussed.




Clinical Pharmacology of Cerebral Ischemia


Book Description

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.




Neurotherapeutics


Book Description

Neuroscience's inherent complexity and rapid growth mean that no one can keep abreast of all the changes across the field. We each bring a necessarily narrow perspective. Neurotherapeutics: Emerg ing Strategies is an attempt to provide some diverse perspectives within the hunt for new drugs to treat central nervous system diseases. The book's premise is that the search for new drugs is based on an understanding ofboth clinical and basic sciences. Neurotherapeu tics: Emerging Strategies begins with psychiatry and concludes with neurological disorders. Each chapter examines a disease, including clinical features and existing treatments, but the emphasis is on current concepts of underlying causes and novel strategies for drug discovery arising from these possible mechanisms. Participating authors include basic neuroscientists, industry-based pharmacolo gists and chemists, and clinicians. The chapters describe the status of the existing disease treat ments, and when treatments are lacking, the approach is more basic science oriented. When there is a long history of treatment, there is greater emphasis on those therapies. However, all the chapters seem to reflect the benefits of cloning, since the availability of receptor subtypes now promises the opportunity for greater specificity of drug effects. Modulation of second messengers is another new and recur ring theme. And in the chapter on cachexia, cytokines are explored both as drugs and drug targets. Neurotherapeutics: Emerging Strategies reflects the complex ity of the nervous system, but the overriding message is hope for new and better drugs to treat those diseases that rob us of ourselves.




Cerebral Ischemia


Book Description

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).




Motor Activity and Movement Disorders


Book Description

In Motor Activity and Movement Disorders thirteen state-of-the-art articles explicate forefront research methodologies for measuring and interpreting motor activity in animals, as well as their applications to preclinical and clinical research involving motor disorders. The contributors emphasize motor asymmetries, turning behavior, and dyskinetic movements. They also present a variety of quantitative approaches designed to assess specific aspects of motor activity and illustrate numerous computerized measuring techniques that permit detailed and objective approaches to quantifying motor behavior. Motor Activity and Movement Disorders will contribute to a greater understanding of brain-behavior relationships through its focus on methodology and its application to current animal models and to human disorders.




Cerebral Signal Transduction


Book Description

Since the pioneering discovery of cyclic AMP four decades ago, a multitude of signaling pathways have been uncovered in which an extracellular signal (first messenger) impacts the cell surface, thereby triggering a cascade that ultimately acts on the cell nucleus. In each cascade the first messenger gives rise to the appearance of a second messenger such as cyclic AMP, cyclic GMP, or diacylglycerol, which in turn triggers a third messenger, a fourth messenger, and so forth. Many advances in elucidating such pathways have been made, including efforts to link messenger molecules to brain processes operative in health or disease. However, the latter type of information, relating signaling pathways to brain function, is scattered across a variety of publication media, which makes it difficult to integrate the multiple roles of different signaling cascades into our understanding of brain function in health and disease. The primary aim of Cerebral Signal Transduction: From First to Fourth Messengers, therefore, is to offer a comprehensive picture of the recent advances made in the signaling field as it relates to neuronal and cere bral function. The current state of progress provides an exciting opportunity for such a comprehensive focus because molecular tools have become available to selectively remove, reduce, or enhance spe cific components in the signaling pathways, e. g. , by interfering with the genes encoding key proteins. In addition, the increased awareness of crosstalk between different signaling cascades has revealed many possibilities for changes in gene expression underlying long-term changes in brain function.