Adult Neurogenesis And Neural Stem Cells In Mammals

This title contains a book and CD. The brain has a number of nerve cells estimated at a magnitude of 10 to 100 billion, and 1014 to 1015 synapses, and therefore is the most complex organ of the human body. During fetal development the foundations of the brain are laid as billions of neurons form appropriate connections and patterns. In the adult mammalian brain, most neurons are post-mitotic, and therefore at risk for irreversible damage. As we age, atrophy of the brain occurs. As brain weight declines the volume of the brain in the 8th decade is reduced by 6 per cent -10 per cent versus the third decade, and neuronal loss occurs, up to 10,000 to 100,000 neurons are lost per day, though this estimation is being revised downward with the advance of more sophisticated measurements.

This text highlights the endogenous regenerative potential of the central nervous system in neonates and juveniles and discusses possible ways it might be manipulated for medical purposes. The first section provides a descriptive summary of the salient steps of human brain development with a discussion of comparisons with other mammalian brains. It also provides a historical perspective on our understanding of ongoing brain development throughout the lifespan and serve to introduce the concept of brain plasticity following injury. The second part is devoted to the endogenous reparative potential of the brain, including its limitations, and articles focusing on defined pathologies (e.g. anoxia/hypoxia, epilepsy, traumatic brain injury and stress) in animal models and in humans pinpoint eventual ways these pathologies might be manipulated. The third and final focuses on the "dark side" of stem cells for brain repair or of the manipulation of spontaneous adaptive events after injury (e.g. genomic instability, sensitization to cancerous transformation and defective neural networks).

This book is a collective work of international experts in the neural stem cell field. The book incorporates the characterization of embryonic and adult neural stem cells in both invertebrates and vertebrates. It highlights the history and the most advanced discoveries in neural stem cells, and summarizes the mechanisms of neural stem cell development. In particular, this book provides strategies and discusses the challenges of utilizing neural stem cells for therapy of neurological disorders and brain and spinal cord injuries. It is suitable for general readers, students, doctors and researchers who are interested in understanding the principles of and new discoveries in neural stem cells and therapy.

Twenty years after the discovery of neural stem cells, the question whether the central nervous system can be considered among regenerative tissues is still open. On one side, deep characterization of neural stem and progenitor cells, their niches, and their progeny in brain neurogenic sites overtly showed that new neurons can be generated in the brain of adult mammals, including humans. On the other side, many problems arise when stem cells encounter the mature brain parenchyma, still hampering the development of efficacious therapeutic approaches with endogenous or exogenously-delivered neural stem cells. This book tries to make the point on these extremely promising, yet unresolved, issues.

The discovery of adult neurogenesis caused a paradigm shift in the neurosciences. For more than 100 years, it was believed that adult neurons do not regenerate. Joseph Altman and Fernando Nottebohm found proof to the contrary and changed the course of history. Their research, included here, provides the foundations of the field. Today, adult neurogenesis is a rapidly expanding discipline applicable to the study of brain development and diseases, learning and memory, aging, and neuropsychiatric disorders. With multiple authors, the 27 chapters of this book contain the latest work in two volumes. The first presents the basic biology of adult neurogenesis in non-mammalian vertebrates and in the mammalian hippocampus and olfactory bulb, and the second discusses clinical implications and delves into adult neurogenesis and brain injury as well as neurodegenerative and neuropsychiatric pathologies. With details of the anatomy, physiology, and molecular biology of the two neurogenic brain regions, this book provides indispensable knowledge for many areas of neuroscience and for experimental and clinical applications of adult neurogenesis to brain therapy.

The discovery that mammalian brains contain neural stem cells which perform adult neurogenesis - the production and integration of new neurons into mature neural circuits - has provided a fully new vision of neural plasticity. On a theoretical basis, this achievement opened new perspectives for therapeutic approaches in restorative and regenerative neurology. Nevertheless, in spite of striking advancement concerning the molecular and cellular mechanisms which allow and regulate the neurogenic process, its exploitation in mammals for brain repair strategies remains unsolved. In non-mammalian vertebrates, adult neurogenesis also contributes to brain repair/regeneration. In mammals, neural stem cells do respond to pathological conditions in the so called "reactive neurogenesis", yet without substantial regenerative outcome. Why, even in the presence of stem cells in the brain, we lack an effective reparative outcome in terms of regenerative neurology, and which factors hamper the attainment of this goal? Essentially, what remains unanswered is the question whether (and how) physiological functions of adult neurogenesis in mammals can be exploited for brain repair purposes.

Adult neurogenesis has been questioned for many years. In the early 1900s, a dogma was established that denied new neuron formation in the adult brain. In the last century however, new discoveries have demonstrated the real existence of proliferation in the adult brain, and in the last decade, these studies led to the identification of neural stem cells in mammals. Adult neural stem cells are undifferentiated cells that are present in the adult brain and are capable of dividing and differentiating into glia and new neurons. Newly formed neurons terminally differentiate into mature neurons in the olfactory bulb and the dentate gyrus of the hippocampus. Since then, a number of new research lines have emerged whose common objective is the phenotypical and molecular characterization of brain stem cells. As a result, new therapies are successfully being applied to animal models for certain neurodegenerative diseases or stroke. At present, and in years to come, this finding extends to the adult human brain, and gives reason and hope to all the previous studies.

After 40 years of research, scientists have confirmed that persistent neurogenesis occurs in the adult mammalian brain. The obvious next question is: "Are the newly generated neurons functional?" If so, "What are the functions of these new neurons?" This volume intends to clarify both questions by providing the latest data available.