Oxidative Neural Injury

Twenty-five years ago, Earl R. Stadtman, PhD discovered that specific enzymes regulating metabolism can be inactivated by oxidation [1]. He later showed that age-related oxidative modification contributes, at least in part, to age-related loss of function of the enzymes [2, 3]. Dr. Stadtman broke the ground for a new field of study to discover how oxidative stress contributes in significant ways to age-related cellular dysfunction and protein accumulation and that oxidation in the aging brain influences Alzheimer’s disease, ischemia-reperfusion injury, amyotrophic lateral sclerosis, and lifespan [4–6]. Today, his research and mentorship have positively influenced the work of hundreds of scientists in this field. We dedicate this book to Dr. Earl R. Stadtman (1912–2008), in celebration of his passion for science and his superior collaborative and mentorship skills. This book is comprised of three sections. The first describes the valuable roles reactive oxygen species (ROS) and reactive nitrogen species (RNS) play in cellular biology. The second section provides an overview of redox imbalance injury with effects on mitochondria, signaling, endoplasmic reticular function, and on aging in general. The third section takes these mechanisms to neurodegenerative disorders and provides a state-of-the-art look at the roles redox imbalances play in age-related susceptibility to disease and in the disease processes. In the first section we attempt to answer a question posed by Dr. Stadtman, ‘‘Why have cells selected reactive oxygen species to regulate cell signaling events’’ [7].

The role of free radicals and oxidative stress in neurological disorders has only recently been recognized, leaving clinical neurologists to seek in vain for information on the subject even in major textbooks. What published information there is may consist of brief reminders of the possible association of superoxidase dismutase with familial amyotrophic lateral sclerosis and nitrous oxide with migraine. With luck they may also find information on the purported role of free radicals in the pathogenesis of traumatic brain injury. Oxidative Stress and Free Radical Damage in Neurology sets the record straight, focusing on clinical and research issues regarding the interplay of free radicals and the human nervous system. Crucially, the chapters cover numerous antioxidants and their possible therapeutic role in neurological disorders. Key illnesses such as epilepsy, multiple sclerosis and Parkinson’s are analyzed, and chapters also examine more general issues such as the link between free radicals and inflammation of the central nervous system. Clinicians and laboratory researchers alike will find that this book augments their understanding not only of the widespread involvement of free radicals in the central nervous system but also of some uncertainties surrounding whether free radical damage in neurology plays a primary or secondary role.

Traumatic brain injury (TBI) accounts for up to one-third of combat-related injuries in Iraq and Afghanistan, according to some estimates. TBI is also a major problem among civilians, especially those who engage in certain sports. At the request of the Department of Defense, the IOM examined the potential role of nutrition in the treatment of and resilience against TBI.

The purpose of this book is to bring together scientists and clinicians interested in oxidative injury in the nervous system but whose approaches to investigation and treatment design vary widely. Indeed the goal of this book is to show that the investiga tive approaches and potential therapeutic interventions perhaps do not vary as widely as some may think. I think that the readers of this book will not read it from front to back, but will pick chapters of interest. Thus, the chapters are organized to contain information that is essential to understanding basic aspects of oxidative injury, and thus have some redundancy. However, within the context of each chapter the reader should hopefully find impetus and direction to go on to another chapter. The book is divided into three seetions. The first section contains reviews of metals and their role in generating oxidative injury. lron is considered in three of these chapters because of its relative abundance in the brain and its potency in inducing free radicals. The second section focuses on mechanisms by which the brain attempts to protect itself from oxidative injury. Some of these mechanisms have the potential to be protective in some situations and potentiaIly damaging in others. The third section contains the clinicaI diseases in which oxidative injury is known to contribute to the pathogenic process. This seetion ends with a chapter on antioxidant therapeutic strate gies in neurological disorders.

Recognition that aging is not the accumulation of disease, but rather comprises fundamental biological processes that are amenable to experimental study, is the basis for the recent growth of experimental biogerontology. As increasingly sophisticated studies provide greater understanding of what occurs in the aging brain and how these changes occur

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 development of new diagnostic and therapeutic approaches has been disappointingly slow. Translational Research in Traumatic Brain Injury attempts to integrate expertise from across specialties to address knowledge gaps in the field of TBI. Its chapters cover a wide scope of TBI research in five broad areas: Epidemiology Pathophysiology Diagnosis Current treatment strategies and sequelae Future therapies Specific topics discussed include the societal impact of TBI in both the civilian and military populations, neurobiology and molecular mechanisms of axonal and neuronal injury, biomarkers of traumatic brain injury and their relationship to pathology, neuroplasticity after TBI, neuroprotective and neurorestorative therapy, advanced neuroimaging of mild TBI, neurocognitive and psychiatric symptoms following mild TBI, sports-related TBI, epilepsy and PTSD following TBI, and more. The book integrates the perspectives of experts across disciplines to assist in the translation of new ideas to clinical practice and ultimately to improve the care of the brain injured patient.

This book deals with basic and clinical aspects of monoamine oxidase (MAO) subtypes A and B highlighting its importance in neurological and psychiatric diseases. Consequently the therapeutic actions of MAO-A and -B inhibitors in Parkinson’s disease (PK) and depression are the focus of several chapters. As MAO is the basis of the development of the "oxidative stress hypothesis" of PD, several chapters are devoted to iron and iron-induced oxidative stress in various experimental studies and clinical conditions. Based on these findings, new compounds have been developed which not only block MAO, but are in addition, either inhibitors of acetylcholine esterase or have iron chelating properties. The aspect of "preclinical" and "clinical" neuro protection as well as MAO neuroprotection are additional topics covered in this book. MAO, iron and neuroprotection are seen in the framework of general anti Parkinson’s therapy with chapters on levodopa, dopaminergic receptor agonists and clinical issues.

Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders. * Contains the latest information on the subject of neurodegenerative disorders * Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems