It is an honor to be asked to write a foreword for this timely book, which assembles contributions from authorities working in the area of pathological nervous system cell death, and has been expertly edited by Vassilis Koliatsos and Rajiv Ratan. That the inap propriate demise of brain or spinal cord cells is at the root of many neurological diseases has been appreciated since the early days of microscopic neuropathology, but it has only been in the last decade or so that pervasive therapeutic nihilism has lifted. In the journey of medical progress, we have reached the shores of a marvelous...

Distinguished medical researchers from around the world review novel neural reconstructive techniques that appear to be beneficial for Parkinson's disease and hold promise for treating Huntington's disease, pain, demyelinating diseases, and stroke. The contributors focus on those diseases for which clinical trials are either ongoing or likely to occur in the near future. Among the topics reviewed are results and rationale for some of the leading transplant programs for the treatment of Parkinson's disease, the use of PET scanning for patient evaluation, autopsy studies of transplant...

In this book, leading-edge investigators offer effective strategies to improve current antidepressive therapies and suggest molecular, biological, and genetic approaches that will lead to the development of novel antidepressants. The contributors' critical reviews and commentaries illuminate our understanding of the mechanism(s) responsible for antidepressant action. The book's goal is to move beyond current biogenic amine-based concepts and therapies to the development of new and improved antidepressants that are more effective and have a more rapid onset than current.

Prominent researchers and clinicians dissect the signaling pathways of an array of neuroprotective factors, ranging from neurotrophins (NGF, BDNF, NT-3, and NT-4/5) to growth factors (bFGF, IGF-1, GDNF), to cytokines (TNF, IL-1b, and TGFb), to secreted amyloid precursor proteins, to protease nexin-1. Also treated are cytoprotective signaling events that occur with injured neurons independently of intercellular signals. In elucidating the molecular cascades evolved by the nervous system to protect itself, the contributors lay the basis for powerful new drug discovery and gene therapy...

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...

A distinguished panel of internationally recognized neuroscientists comprehensively review the involvement of and changes in glial cells both during the normal aging process and in the major disorders of old age. Topics range from the cellular and molecular changes that occur with aging-especially aging-associated activation of astrocytes and microglia and its relation to neuronal injury and repair-to neuron-glia intercommunication. The contributors show how glial signals may be modulated by hormones, growth factors, neurotransmitters, intracellular metabolism, and intercellular exchanges, as...

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...

Distinguished researchers review the latest scientific understanding of spinal cord injury (SCI), focusing on the mechanisms causing paralysis after spinal cord trauma, the molecular determinants of neural regeneration, and methods for improving damaged function. The authors examine the role of intracellular Ca2+ in neuronal death, the possibility of spinal learning, growth-promoting molecules for regenerating neurons, and the biochemistry and cell biology of microtubules. Among the treatment possibilities discussed are cell transplantation strategies beyond the use of fetal spinal cord...

Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer's, Parkinson's, and Huntington's diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative,...

Mitochondria have long been the Rodney Dangerfield of cellular organelles. Believed to be the remnants of bacterial infection of eukaryotic cells eons ago, the mitochondrion evolved a symbiotic relationship in which it dutifully served as the efficient source of A TP for cell function. The extraordinary dependence of cells on the energy provided by mito chondrial oxidative metabolism of glucose, especially through critical organs such as the heart and brain, is underlined by the fatal consequences of toxins that interfere with the mitochondrial electron transport system. Consistent with their...