Pharmacological Approaches to the Treatment of Brain and Spinal Cord Injury PDF
Preview Pharmacological Approaches to the Treatment of Brain and Spinal Cord Injury
PHARMACOLOGICAL ApPROACHES TO THE TREATMENT OF BRAIN AND SPINAL CORD INJURY PHARMACOLOGICAL ApPROACHES TO THE TREATMENT OF BRAIN AND SPINAL CORD INJURY EDITED BY DONALD G. STEIN Clark University Worcester, Massachusetts AND BERNHARD A. SABEL University of Munich Munich, Federal Republic of Germany PLENUM PRESS. NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Luxembourg Conference on Recovery from Brain and Spinal Cord Injury (2nd: 1986: Walferdange, Luxembourg) Pharmacological approaches to the treatment of brain and spinal cord injury. "Based on the Second Luxembourg Conference on Recovery from Brain and Spinal Cord Injury, held July 7 -11, 1986, in Walferdange, Luxembourg" - T . p. verso. Includes bibliographies and index. 1. Brain damage-Chemotherapy-Evaluation-Congresses. 2. Spinal cord Wounds and injuries-Chemotherapy-Evaluation-Congresses. I. Stein, Donald G. II. Sabel, Bernhard A. III. Title. [DNLM: 1. Brain Injuries - drug therapy - congresses. 2. Spinal Cord Injuries - drug therapy - congresses. WL 354 L977 1986pj RC387.5.L89 1986 617'.481061 88-5942 ISBN-13: 978-1-4612-8249-5 e-ISBN-13: 978-1-4613-0927-7 DOl: 10.1007/978-1-4613-0927-7 Based on the Second Luxembourg Conference on Recovery from Brain and Spinal Cord Injury, held July 7-11, 1986, in Walferdange, Luxembourg © 1988 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1988 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher To Darel and Liz CONTRIBUTORS YOSEF BAWNIK • Department of Neurobiology, The Weizmann In stitute of Science, Rehovot, Israel 76100 MICHAEL S. BEATTIE • Departments of Surgery (Neurologic Sur gery) and Anatomy, and Spinal Cord Injury Research Center, The Ohio State University, Columbus, Ohio 43210 MICHAEL BELKIN • Goldschleger Eye Institute, Tel Aviv University, Tel Hashomer, Israel SIM6N BRAILOWSKY • National Institute of Sciences and Technology, D.I.F., Mexico 14000 D.F., Mexico. Present address: Laboratory of Neurophysiology, C.N.R.S., 91190 Gif sur Yvette, France JACQUELINE C. BRESNAHAN • Departments of Surgery (Neurologic Surgery) and Anatomy, and Spinal Cord Injury Research Center, The Ohio State University, Columbus, Ohio 43210 R. DAL Toso • Fidia Research Laboratories, 35031 Abano Terme, Italy PAUL DE KONING • Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, and Institute of Molecular Bi ology and Medical Biotechnology, University of Utrecht, 3584 CH Utrecht, The Netherlands PAUL DELREE • Department of Human Physiology and Phys iopathology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium PAUL DEMEDIUK • Department of Neurology, University of Califor nia, San Francisco, and Center for Neural Injury, Veterans Admin istration Medical Center, San Francisco, California 94121 GARY L. DUNBAR • Brain Research Laboratory, Department of Psy chology, Clark University, Worcester, Massachusetts 01610. Present address: Department of Psychology, Central Michigan Univer sity, Mt. Pleasant, Michigan 48852 ALAN I . FADEN • Department of Neurology, University of California, San Francisco, and Center for Neural Injury, Veterans Administra tion Medical Center, San Francisco, California 94121 VII VlII CONTRIB UTORS DENNIS M. FEENEY • Departments of Psychology and Physiology, The University of New Mexico, Albuquerque, New Mexico 87131 G. FERRARI • Fidia Research Laboratories, 35031 Abano Terme, Italy WILLEM HENDRIK GISPEN • Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, and Institute for Mo lecular Biology and Medical Biotechnology, University of Utrecht, 3584 CH Utrecht, The Netherlands ADRIAN HAREL • Department of Neurobiology, The Weizmann In stitute of Science, Rehovot, Israel 76100 FRANZ HEFTI • Department of Neurology, University of Miami School of Medicine, Miami, Florida 33101 STEPHEN E. KARPIAK • Division of Neuroscience, New York State Psychiatric Institute, and Departments of Psychiatry and Biochemis try and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032 ANDREW KERTESZ • Research Institute, St.Joseph's Hospital, Univer sity of Western Ontario, London, Ontario N6A 4V2, Canada VERED LAVIE • Department of Neurobiology, The Weizmann In stitute of Science, Rehovot, Israel 76100 PHILIPPE P. LEFEBVRE • Department of Human Physiology and Phys iopathology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium A. LEON • Fidia Research Laboratories, 3503 i Abano Terme, Italy PIERRE LEPRINCE • Department of Human Physiology and Pa thophysiology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium Yu S. LI • Division of Neuroscience, New York State Psychiatric In stitute, and Departments of Psychiatry and Biochemistry and Mo lecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032 SAHEBARAO P. MAHADIK • Division of Neuroscience, New York State Psychiatric Institute, and Departments of Psychiatry and Biochemis try and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032 TRACY K. McINTOSH • Department of Neut'ology, University of Cal ifornia, San Francisco, and Center for Neural Injury, Veterans Ad ministration Medical Center, San Francisco, California 94121. Present address: Laboratory for Neuroscience Research, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut 06032 CONTRIBUTORS IX GUSTAVE MOONEN • Department of Human Physiology and Phys iopathology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium MANUEL N IETO-SAMPEDRO • Department of Psychobiology, U niver sity of California at Irvine, Irvine, California 92717 VIVIANE PALLAGE • Department of Neurophysiology and Biology of Behavior, Center of Neurochemistry, C.N.R.S., 67084 Strasbourg, France JEAN-MICHEL RIGO • Department of Human Physiology and Pa thophysiology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium BERNARD ROGISTER • Department of Human Physiology and Pa thophysiology, University of Liege, Institute L. Fredericq, B-4020 Liege, Belgium BERNHARD A. SABEL • Institute of Medical Psychology, University of Munich, School of Medicine, 8000 Munich 2, Federal Republic of Germany MICHAL SCHWARTZ • Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel 76100 S. D. SKAPER • Fidia Research Laboratories, 35031 Abano Terme, Italy, and Department of Biology and School of Medicine, Univer sity of California at San Diego, La Jolla, California 92093 ARIE SOLOMON • Goldschleger Eye Institute, Tel Aviv University, Tel Hashomer, Israel DONALD G. STEIN • Departments of Psychology and Biology, Clark University, Worcester, Massachusetts 01610. Present address: Dean of the Graduate School and Associate Provost for Research, Rutgers University at Newark, Newark, New Jersey 07102 CATHY STEIN-IzSAK • Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel 76100 BRADFORD T. STOKES • Departments of Surgery (Neurologic Sur gery) and Anatomy, and Spinal Cord Injury Research Center, The Ohio State University, Columbus, Ohio 43210 RICHARD L. SUTTON • Departments of Psychology and Physiology, The University of New Mexico, Albuquerque, New Mexico 87131 G. TOFFANO • Fidia Research Laboratories, 35031 Abano Terme, Italy GUY TONIOLO • Department of Neurophysiology and Biology of Be havior, Center of Neurochemistry, C.N.R.S., 67084 Strasbourg, France G. V ANTINI • Fidia Research Laboratories, 35031 Abano Terme, Italy WILLIAM J. WEINER • Department of Neurology, University of Miami School of Medicine, Miami, Florida 33101 x CONTRIBUTORS BRUNO WILL • Department of Neurophysiology and Biology of Be havior, Center of Neurochemistry, C.N.R.S., 67084 Strasbourg, France JUSTIN A. ZIVIN • Department of Neurology, San Diego Veterans Administration Medical Center, and Department of Neurosciences, University of California, San Diego, La Jolla, California 92093 PREFACE Although there are over 400,000 people each year in the United States alone who suffer from traumatic injury to the central nervous system (CNS), no phar macological treatment is currently available. Considering the enormity of the problem in terms of human tragedy as well as the economic burden to families and societies alike, it is surprising that so little effort is being made to develop treatments for these disorders. Although no one can become inured to the victims of brain or spinal cord injuries, one reason that insufficient time and effort have been devoted to research on recovery is that it is a generally held medical belief that nervous system injuries are simply not amenable to treatment. At best, current therapies are aimed at providing symptomatic relief or focus on re habilitative measures and the teaching of alternative behavioral strategies to help patients cope with their impairments, with only marginal results in many cases. Only within the last decade have neuroscientists begun to make serious inroads into understanding and examining the inherent "plasticity" found in the adult CNS. Ten years or so ago, very few researchers or clinicians would have thought that damaged central neurons could sprout new terminals or that intact nerve fibers in a damaged pathway could proliferate to replace inputs from neurons that died as a result of injury. It would have been even more radical to propose that specific phar macological agents might serve to salvage or spare brain or spinal neurons from the devastating effects of traumatic injury. Anyone who proposed that injured brains produce special proteins that enhance neuronal survival and promote new axonal growth, or that glial cells may playa pivotal role in the enhancement of functional recovery from CNS trauma, would have found his scientific cred ibility at stake. Today, neuroscience is in the midst of a scientific revolution. Long-held beliefs and research paradigms are being seriously reevaluated in the face of new discoveries about the nature of neuronal and glial plasticity in the central nervous system. These discoveries are dramatically altering the way we think about recovery and are permitting, for the first time, some optimism that brain injury might be treated with pharmacological agents. Both of us have studied various ways of promoting recovery from severe brain injuries, and in the course of our research, we realized that there was no XI xii PREFACE current overview of this important field. In July, 1986, an international con ference on experimental approaches to the treatment of brain and spinal cord injuries was held in Walferdange, Luxembourg. A number of American and European colleagues who have been deeply concerned with finding the means to promote functional recovery from brain and spinal injuries were invited to dis cuss and share their research findings in an informal, collegial setting. The present volume summarizes the contemporary research in this area, ranging from clinical neuropsychology to the possible role of oncogenes in neuroplasticity. Each of the participants brought a special expertise to discuss. Some investigators were primarily concerned with neurotransmitter biochemistry in the brain or spinal cord and the alterations that occurred after injury; others discussed the question of how endogenous or exogenous "trophic" substances might work to promote survival of damaged neurons or new axonal growth. We also invited colleagues who sought to determine how some of the secondary damage that accompanies CNS injury could be characterized and prevented. Finally, there were others with behavioral concerns who were interested in determining whether new, experimental substances could be used to enhance cognitive and functional recovery after traumatic brain injury. As with previous Clark University/Luxembourg meetings, this one, too, was made possible through the generosity of Mr. Henry J. Leir, a Clark Univer sity benefactor who has long been interested in fostering international coopera tion in the sciences and the humanities. We were also fortunate to receive generous grants from the following pharmaceutical companies that enabled us to bring colleagues to Luxembourg from ten countries. We wish to thank Fidia Research Laboratories of Italy; P.F. Medicament, France; American Cyanamid, U.S.A.; Schering, AG, Fed. Rep. Germany; Abbott Laboratories, U.S.A.; Cybila, GmBH, Fed. Rep. Germany; Travenol Laboratories, U.S.A.; Eli Lilly & Company, U.S.A.; and E.!. DuPont Pharmaceuticals, U.S.A., for their support, interest, and encouragement of this meeting. As was the case in the past, we were very happy to have the continued support of Dr. Gaston Schaber, Luxembourg Ministry of Education, as well as the kindness and hospitality of the Mayor of Walferdange and the excellent staff of the Institute Pedagogique, who did everything in their power to ensure a successful and pleasant meeting; we eagerly look forward to future collabora tions with them. Finally, we owe a warm and grateful "thank you" to our respective spouses, Darel Stein and Elizabeth Sabel, for their unswerving support and patience through the good and the bad times. D.G.S., B.S. Worcester, Massachusetts
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