New Concepts in Cerebral Ischemia PDF

Preface

Every year more than a half million American suffer from stroke. At present, stroke is the third leading cause of death in the U.S. and is the number one cause of disability. With the rapid growth of the elderly population, brain attack constitutes a major healthcare concern, even in our highly competitive and developed modern-day society. In the United State alone, the estimated annual cost for healthcare may exceed an alarming fifty billion dollars. Despite our extensive research efforts to better understand the biological mechanisms of stroke-induced neuronal injury in animal models, a promising drug which protects neurons from various types of insult remains unavailable for clinical application. However, our endeavors have not gone unrewarded. In fact, multi-disciplinary approaches in search of a neuroprotective therapy have lead to many novel findings, and have provided investigators with valuable insight. With continuing progress, it is foreseeable that in the near future effective treatments for neuron survival will be a reality.

The main goal of this book is to provide a detailed description of the various mechanisms involved in neuronal degeneration and the glial response to stroke and/or traumatic brain injury. There is an additional emphasis on potential strategies which may prove beneficial for neuroprotection following ischemic insult or a damage-inducing event.

Eleven chapters are included in this book. Over the years, gender-dependent differences have been observed in response to neurological insult. Chapter 1 deals specifically with this issue, and provides a current view as well as experimental data for illustration purposes. Birth asphyxia can cause severe cerebral ischemic injury, and result in a lifetime of reduced mental as well as physical capacity. Chapter 2 introduces this topic and considers processes which elicit neonatal neuron death. The transplantation of stem cells for various types of CNS disease has been examined recently as a candidate approach for function restoration after brain injury. To address this exciting area of research, chapter 3 provides an overview of new findings and elaborates on the future implementation of this application after stroke. Chapter 4 presents issues related to excitotoxicity, oxidative stress, and apoptosis. Chapters 5 and 6 introduce new data and current ideas on the role of calcium and zinc in neuronal death. Adenosine related compounds have been utilized extensively for cardiac ischemia, but have not yet been adopted as a means for limiting the development and severity of neurological lesions. Chapter 7 provides a rationale for the inability of adenosine and its corresponding receptors to produce a beneficial neuroprotective effect in human stroke victims. Chapter 8 summarizes the cellular and molecular events triggered by calpain and caspase in ischemic as well as traumatic brain injury. The brain immune response has attracted a lot of attention. Chapter 9 provides the reader with a new, detailed view which favors the future usage of anti-inflammatory agents to improve neurological outcome following episodes of ischemia. Chapter 10 addresses the fundamentals of hyperbaric oxygen therapy as a potential means to prevent neuronal damage. Lastly, one of the most frustrating aspects associated with hypoxia is the lack of consensus regarding transient ischemic attack. Chapter 11 describes experimental models and recent advances in an area that has received little attention.

Looking back over 40 years upon the painful memory of a child who lost his grandfather to stroke, I am privileged to have had the opportunity to further understand this devastating disease and contribute to a scientific community whose talented members are rapidly advancing along many fronts to provide hope for many. At this time, I would like to express my sincere appreciation to all of my colleagues who have shaped my professional career and influenced my research interests. First, I would like to thank my previous Duke University colleagues, Drs. Jim Davis, Barbara Crain, and Vic Nadler for introducing me to this gratifying field of study. Second, I would like to thank my good friends and colleagues, Drs. Miguel Nicolelis and Sidney Simon, also at Duke, for their endorsement of this publication and support throughout its assembly. Finally, I extend my gratitude to Barbara Norwitz, a senior editor from CRC, for her patience and commitment to this project.