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Axonal Regeneration in the Central Nervous Syst. - N. Ingoglia, M. Murray (Marcel Dekker, 2001) WW PDF

735 Pages·2001·70.92 MB·English
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Axonal Regeneration in the Central Nervous System NEUROLOGICAL DISEASE AND THERAPY Advisory Board Louis R. Caplan, M.D. Professor of Neurology Harvard University School of Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts William Koller, M.D. National Parkinson Foundation Miami, Florida John C. Morris, M.D. Friedman Professor of Neurology Co-Director, Alzheimer’s Disease Research Center Washington University School of Medicine St. Louis, Missouri Jerome Murphy, M.D. Professor of Neurology University of Missouri School of Medicine Chief of Neurology Children’s Mercy Hospital Kansas City, Missouri Kapil Sethi, M.D. Professor of Neurology Director, Movement Disorders Program Medical College of Georgia Augusta, Georgia Mark Tuszynski, M.D., Ph.D. Associate Professor of Neurosciences Director, Center for Neural Repair University of California - San Diego La Jolla, California 1. Handbook of Parkinson’s Disease, edited by William C. Keller 2. Medical Therapy of Acute Stroke, edited by Mark Fisher 3. Familial Alzheimer’s Disease: Molecular Genetics and Clinical Per- spectives, edited by Gary D. Miner, Ralph W. Richter, John P. B/ass, Jimmie L. Valentine, and Linda A. Winters-Miner 4. Alzheimer’s Disease: Treatment and Long-Term Management, edited by Jeffrey L. Cummings and Bruce L. Miller 5. Therapy of Parkinson’s Disease, edited by William C. Keller and George Paulson 6. Handbook of Sleep Disorders, edited by Michael J. Thorpy 7. Epilepsy and Sudden Death, edited by Claire M. Lathers and Paul L. Schraeder 8. Handbook of Multiple Sclerosis, edited by Stuart D. Cook 9. Memory Disorders: Research and Clinical Practice, edited by Takehiko Yanagihara and Ronald C. Petersen 10. The Medical Treatment of Epilepsy, edited by Stanley R. Resor, Jr., and Henn Kutt 11. Cognitive Disorders: Pathophysiology and Treatment, edited by Leon J. Thai, Walter H. Moos, and Elkan R. Gamzu 12. Handbook of Amyotrophic Lateral Sclerosis, edited by Richard A/an Smith 13. Handbook of Parkinson’s Disease: Second Edition, Revised and Ex- panded, edited by William C. Ko//er 14. Handbook of Pediatric Epilepsy, edited by Jerome V. Murphy and Ferey- doun Dehkharghani 15. Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders, edited by Roger K&an 16. Handbook of Cerebellar Diseases, edited by Richard Lechtenberg 17. Handbook of Cerebrovascular Diseases, edited by Harold P. Adams, Jr. 18. Parkinsonian Syndromes, edited by Matthew B. Stem and William C. Keller 19. Handbook of Head and Spine Trauma, edited by Jonathan Greenberg 20. Brain Tumors: A Comprehensive Text, edited by Robert A. Moran& and John W. Walsh 21. Monoamine Oxidase Inhibitors in Neurological Diseases, edited by Abra- ham Lieberman, C. Warren Olanow, Moussa 6. H. Youdim, and Keith Tipton 22. Handbook of Dementing Illnesses, edited by John C. Mom% 23. Handbook of Myasthenia Gravis and Myasthenic Syndromes, edited by Robert P. Lisak 24. Handbook of Neurorehabilitation, edited by David C. Good and James R. Couch, Jr. 25. Therapy with Botulinum Toxin, edited by Joseph Jankovic and Mark Hallett 26. Principles of Neurotoxicology, edited by Louis W. Chang 27. Handbook of Neurovirology, edited by Robert R. McKenda// and William G. Stroop 28. Handbook of Neuro-Urology, edited by David N. Rushton 29. Handbook of Neuroepidemiology, edited by Philip 13. Gorelick and Milton Alter 30. Handbook of Tremor Disorders, edited by Leslie J. Findley and William C. Keller 31. Neuro-Ophthalmological Disorders: Diagnostic Work-Up and Management, edited by Ronald J. Tusa and Steven A. Newman 32. Handbook of Olfaction and Gustation, edited by Richard L. Doty 33. Handbook of Neurological Speech and Language Disorders, edited by Howard S. Kirshner 34. Therapy of Parkinson’s Disease: Second Edition, Revised and Ex- panded, edited by William C. Keller and George Paulson 35. Evaluation and Management of Gait Disorders, edited by Barney S. Spivack 36. Handbook of Neurotoxicology, edited by Louis W. Chang and Robert S. Dyer 37. Neurological Complications of Cancer, edited by Ronald G. Wiley 38. Handbook of Autonomic Nervous System Dysfunction, edited by Amos D. Korczyn 39. Handbook of Dystonia, edited by Joseph King Ching Tsui and Donald B. Calne 40. Etiology of Parkinson’s Disease, edited by Jonas l-l. Ellenberg, William C. Keller, and J. William Langston 41. Practical Neurology of the Elderly, edited by Jacob I. Sage and Margery H. Mark 42. Handbook of Muscle Disease, edited by Russell J. M. Lane 43. Handbook of Multiple Sclerosis: Second Edition, Revised and Expanded, edited by Stuart D. Cook 44. Central Nervous System Infectious Diseases and Therapy, edited by Karen L. Roos 45. Subarachnoid Hemorrhage: Clinical Management, edited by Takehiko Yanagihara, David G. Piepgras, and John L. D. Atkinson 46. Neurology Practice Guidelines, edited by Richard Lechtenberg and Henry S. Schutta 47. Spinal Cord Diseases: Diagnosis and Treatment, edited by Gordon L. Angler, Jonathan Cole, and W. Louis Merton 48. Management of Acute Stroke, edited by Ashfaq Shuaib and Larry B. Goldstein 49. Sleep Disorders and Neurological Disease, edited by Antonio Culebras 50. Handbook of Ataxia Disorders, edited by Thomas Klockgether 51. The Autonomic Nervous System in Health and Disease, David S. Goldstein 52. Axonal Regeneration in the Central Nervous System, edited by Nicholas A. lngoglia and Marion Murray Additional Volumes in Preparation Handbook of Multiple Sclerosis: Third Edition, edited by Stuart D. Cook Axonal Regeneration in the Central Nervous System edited by Nicholas A. Ingoglia New Jersey Medical School-UMDNJ Newark, New Jersey Marion Murray Medical College of Pennsylvania/Hahnemann University Philadelphia, Pennsylvania MARCEL zs MARCEL DEKKER, INC. N DEKKER NEW YORK l BASEL ISBN: o-8247-041 O-X This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 2 12-696-9000; fax: 2 12-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 8 12, CH-400 1 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more infor- mation, write to Special Sales/Professional Marketing at the headquarters address above. Copyright 0 2001 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechamcal, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permissron in writmg from the publisher. Current printing (last digtt): 10987654321 PRINTED IN THE UNITED STATES OF AMERICA AUTHOR’S NOTE The work described in these chapters summarizes the current state of research into regeneration of axons in the Central Nervous System of vertebrates. We need to remember that these advances are the result of basic scientific research carried out by dedicated scientists in all fields of biology, even those apparently distant from the issues of regeneration research. The remarkable developments in this research give hope that greatly improved treatments for brain and spinal cord injuries will soon be available. Indeed this work has also been stimulated by the appreciation that we have for those who suffer from the devastating consequences of brain and spinal injury and for their families. We would like to dedicate this volume to those individuals - to the famous, such as Christopher Reeve, whose unstinting efforts to raise awareness of the emotional, physical and monetary costs of spinal injury have been so important to the recent advancement of the research efforts, and to the less famous, such as Adam Shapiro, a boy struggling to recover and rebuild a life after his spinal injury, who has reminded us of the courage, the hope, and ef- fort and ultimately the optimism that this requires and who recently sent us this note: t;li. My name is Adam Shapiro and I am 15 years old In September of 1996 I broke my neck (C3-C4) leaving me an incomplete quadriplegic. My mom and I check the Internet every day to see if there is any new information on spinal cord nerve regeneration. I have come a long way. I started off on a ventilator, and could not move anything. It took me three months to get off the ventilator, and that is when I started conditioning my body. At this time I am able to walk with a walker, but my arms are considerably weaker than my legs.. If you could please e-mail me back, I am very anxious to get involved in new treatments that you are conducting now on humans, I would greatly appreciate it, or tf not please keep me in mind in the future. Thank you so much for your time.. . Finally, on a more personal note, we would like to dedicate this volume to our friend, our teacher, our mentor and our colleague, Bernice Grafstein, who led us into this field and so changed our scientific lives. This Page Intentionally Left Blank PREFACE One of the most fundamental questions in neuroscience is why certain neurons respond to axotomy by robustly regrowing a new axon while others do not. This basic difference between neurons in lower vertebrates and mammalian peripheral nerves on the one hand, and nerves found in the central nervous system (CNS) of mammals on the other, has been the launching pad for the experimental lives of countless former and current researchers and in many cases has led to lifelong commitments to try to understand this elemental fact of neural life. What is per- haps most vexing about our inability to understand the reasons why mammalian central neurons fail to regenerate following injury is the enormous impact this has on the human condition. Each year thousands of patients become victims of brain or spinal cord injuries resulting in varying degrees of cognitive loss or paralysis. Once these neurons have been severed they are not likely to recover. To these pa- tients we can, at present, offer little in the way of treatment. But we offer much in the way of hope. The hope springs from the enormous progress that has been made in the past 30 or so years in understanding the molecular and cellular events occur- ring in systems that are successful in regenerating new axons and, more recently, in the analysis of mammalian central neurons where abortive regeneration and cell death are still the general consequences of axotomy but where there is now clear evidence for regrowth following certain experimental interventions. Our view of the scientific problem and thus our approach to solving it, has been shaped in large part by the studies of Santiago Ramon y Cajal (1928) who wrote in the early part of this century: “My observations, made in the optic nerve and spinal cord...demonstrated also that the incapability of regeneration is not a fatally irresistible law, but is a secondary outcome of a physical or chemical environment unfavorable for the growth of the sprouts.... ” These observations focused our thoughts and research strategies on the glial barriers (“scars”) to nerve growth. But we know today that, while an impenetrable barrier (or inhibitory pro- teins on the membranes of cells in the region of the injury) is likely to play an im- portant role in the failure of a neuron to grow a new axon, other factors such as cell survival, the genetic growth program of the darnaged neuron, the response of neurons to growth and guidance factors and, perhaps, the failure of a cut axon to reseal may all play roles in the successful regrowth of a new axon. As was true for Cajal, modern researchers have generally favored the optic nerve and spinal cord as models to study the issue of axonal regeneration and recovery of function, and the contributions in this volume largely reflect those models. We believe, how- ever, that the lessons learned from the optic nerve and spinal cord are general&- able to other parts of the CNS. The goal of this book is to summarize some of the major research contri- butions in nerve regeneration reported over the past 30 years and then show how these discoveries have led to the current strategies to promote axonal regeneration

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