Monographs on Pathology of Laboratory Animals

Sponsored by the International Life Sciences Institute

Editorial Board

J.D. Burek, West Point· J. S. Campbell, Ottawa C. C. Capen, Columbus · A. Cardesa, Barcelona R. G. Carlson, Kalamazoo· D. de Paola, Rio de Janeiro G. Della Porta, Milan· J . L. Emerson, Atlanta F. M. Gamer, Rockville· L. Golberg, Research Triangle Park H. C. Grice, Nepean ·C. C. Harris, Bethesda· R. Hess, Basel C. F. Hollander, Riom ·G. H. Hottendorf, Charleston R. D. Hunt, Southborough · T. C. Jones, Southborough Y. Konishi, Nara ·D. Krewski, Ottawa· R. Kroes, Bilthoven H. Luginbuhl, Bern· U. Mohr, Hannover· P. Olsen, Harare J. A. Popp, Research Triangle Park· J. R. Schenken, Omaha R. A. Squire, Baltimore· J. Sugar, Budapest S. Takayama, Tokyo· G. C. Todd, Greenfield L. Tomatis, Lyon· B. F. Trump, Baltimore ·J.M. Ward, Frederick

Officers - !LSI

Alex Malaspina, Atlanta - President Peter B. Dews, Boston - Vice President Ulrich Mohr, Hannover - Vice President Roger D. Middlekauff, Washington - Secretary/Treasurer

The following volumes have appeared so far

Endocrine System 1983. 346 figures. XV, 366 pages. ISBN 3-540-11677-X

Respiratory System 1985. 279 figures. XV, 240 pages. ISBN 3-540-13521-9

Digestive System 1985. 352 figures. XVIII, 386 pages. ISBN 3-540-15815-4

Urinary System 1986. 362 figures. XVIII, 405 pages. ISBN 3-540-16591-6

Genital System 1987. 340 figures. XVII, 304 pages. ISBN 3-540-17604-7

The following volumes are in preparation

Integument and Mammary Gland Hemopoietic System Musculoskeletal System Cardiovascular System Special Sense

T.C.Jones U.Mohr R.D.Hunt (Eds.)

Nervous System

With 242 Figures and 12 Tables

Springer-Verlag Berlin Heidelberg GmbH

Thomas Carlyle Jones, D.V.M., D. Sc. Professor of Comparative Pathology, Emeritus Harvard Medical School New England Regional Primate Research Center One Pine Hill Drive, Southborough, MA 01772, USA

Ulrich Mohr, M.D. Professor of Experimental Pathology Medizinische Hochschule Hannover lnstitut fur Experimentelle Pathologie Konstanty-Gutschow-Strasse 8 3000 Hannover 61, Federal Republic of Germany

Ronald Duncan Hunt, D.V.M. Professor of Comparative Pathology Harvard Medical School New England Regional Primate Research Center One Pine Hill Drive, Southborough, MA 01772, USA

Library of Congress Cataloging-in-Publication Data. Nervous system I T.C.Jones, U.Mohr, R. D. Hunt (eds.). p. em. - (Monographs on pathology of laboratory animals) Includes bibliographies and index. ISBN 0-387-19416-9 (U.S.) 1. Nervous system - Diseases - Animal models. I. Jones, Thomas Carlyle. II. Mohr, U. (Ulrich) III. Hunt, Ronald Duncan. IV. Series. [D NLM: 1. Animals, Laboratory. 2. Nervous System Diseases - pathology. 3. Nervous System Diseases - veterinary. 4. Nervous System Neoplasms -pathology. WL 100 N4561] RC337.N46 1988 616.8'0072'4- dc19 DNLM/DLC 88-24760

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© Springer-Verlag Berlin Heidelberg 1988 Softcover reprint of the harcover 1st edition 1988

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ISBN 978-3-642-83518-6 ISBN 978-3-642-83516-2 (eBook) DOI 10.1007/978-3-642-83516-2

Foreword

The International Life Sciences Institute (ILSI) was estab­lished in 1978 to stimulate and support scientific research and educational programs related to nutrition, toxicology, and food safety, and to encourage cooperation in these programs among scientists in universities, industry, and government agencies to assist in the resolution of health and safety issues. To supplement and enhance these efforts, ILSI has made a major commitment to supporting programs to harmon­ize toxicological testing, to advance a more uniform inter­pretation of bioassay results worldwide, to promote a common understanding of lesion classifications, and to encourage wide discussion of these topics among scien­tists. The Monographs on the Pathology of Laboratory Ani­mals are designed to facilitate communication among those involved in the safety testing of foods, drugs, and chemicals. The complete set will cover all organ systems and is intended for use by pathologists, toxicologists, and others concerned with evaluating toxicity and carcinogen­icity studies. The international nature of the project - as reflected in the composition of the editorial board and the diversity of the authors and editors - strengthens our ex­pectations that understanding and cooperation will be im­proved worldwide through the series.

Alex Malaspina President International Life Sciences Institute

Preface

This book, on the nervous system, is the sixth volume of a set pre­pared under the sponsorship of the International Life Sciences Insti­tute (ILSI). One aim of this set on the Pathology of Laboratory Ani­mals is to provide information which will be useful to pathologists, especially those involved in studies on the safety of foods, drugs, chemicals, and other substances in the environment. It is expected that this and future volumes will contribute to better communication, on an international basis, among people in government, industry, and academia who are involved in protection of the public health. The arrangement of this volume is based, in part, upon the philoso­phy that the first step toward understanding a pathologic lesion is its precise and unambiguous identification. The microscopic and ultra­structural features of a lesion that are particularly useful to the pa­thologist for definitive diagnosis, therefore, are considered foremost. Diagnostic terms preferred by the author and editors are used as the subject heading for each pathologic lesion. Synonyms are listed, al­though most are not preferred and some may have been used errone­ously in prior publications. The problems arising in the differential diagnosis of similar lesions are considered in detail. The biologic sig­nificance of each pathologic lesion is considered under such headings as etiology, natural history, pathogenesis, and frequency of occur­rence under natural or experimental conditions. Comparison of information available on similar lesions in man and other species is valuable as a means to gain broader understanding of the processes involved. Knowledge of this nature is needed to form a scientific basis for safety evaluations and experimental pathology. References to pertinent literature are provided in close juxtaposition to the text in order to support conclusions in the text and lead toward additional information. Illustrations are an especially important means of nonverbal communication, especially among pathologists, and therefore constitute important features of each volume. The subject under each heading is covered in concise terms and is ex­pected to stand alone, but in some instances it is important to refer to other parts of the volume. A comprehensive index is provided to en­hance the use of each volume as a reference. Some omissions are inevitable and we solicit comments from our col­leagues to identify parts which need strengthening or correcting. We have endeavored to include important lesions which a pathologist might encounter in studies involving the rat, mouse, or hamster. New­ly recognized lesions or better understanding of old ones may make revised editions necessary in the future. The editors wish to express our deep gratitude to all of the individu­als who have helped with this enterprise. We are indebted to each au­thor and member of the Editorial Board whose names appear else­where in the volume. We are especially grateful to the Officers and Board of Trustees of the International Life Sciences Institute for their support and understanding. Several people have worked directly on important details in this venture. These include Mrs. Nina Murray,

VIII Preface

Executive Secretary; Mrs. Ann Balliett, Editorial Assistant; Mrs. June Armstrong, Medical Illustrator; Mrs. Katie A. Parker, Secretary; and Mrs. Virginia Werwath, Administrative Assistant. Ms. Sharon K. Coleman, ILSI Coordinator for External Affairs, Ms. Karen A. Taylor, ILSI Manager, Publications, and Ms. Sharon Senzik, Ad­ministrator of the ILSI Washington office, were helpful on many oc­casions. We are particularly grateful to Dr. Dietrich Gotze and his staff at Springer-Verlag for the quality of the published product.

June 1988 THE EDITORS

T.C.Jones U. Mohr R.D.Hunt

Table of Contents

General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Microvasculature in Experimental Glioma and Developing Brain, Rat Y. YOSHIDA and F. IKUTA . . . . . . . . . . . . . . . . . . . 1

Experimental Allergic Encephalomyelitis, Rat B.RYFFEL .. .... ... .. .... .... . . 6

Effects of Neurotoxins . . . . . . . . . . . . . . . . . . . . . . . . 17

Neurotoxic Effects of Pyridoxine (Megavitaminosis B6), Rat G.J.KRINKE . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Neurotoxic Effects of Doxorubicin, Rat B.S.JORTNER ....... . ...... . ......... 25

Neurotoxic Effects of Clinoquinol, Mouse M. KOGA, J. TATEISHI, Y.SATO, and K. MATSUKI 29

Neurotoxic Effects of Hexacarbons (n-Hexane, M ethyl-n-Butylketones; 2,5-Hexane-Dione; 1,4-Diketones) G.STOLTENBURG-DIDINGER and H. ALTENKIRCH . . . . 32

Organophosphorus Ester-Induced Delayed Neuropathy, Rat B.S.JORTNER . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Neurotoxic Effects of Ethidium Bromide, Rat K. SUZUKI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Neurotoxic Effects of 6-Aminonicotinamide, Mouse H.AIKAWA and K.SUZUKI ..................... 53

Neurotoxic Effects of Trimethyltin G.J. KRINKE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58.

Neurotoxic Effects of Lysolecithin, Mouse, Rat S.M. HALL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Neurotoxicity of Perhexiline Maleate in Rats Y. HAY ASH!, A. MAEKA W A, and S. YOSHIMURA . . . . . . . . . 74

Cycloleucine Encephalopathy, Rats and Mice H.C.POWELL . . . . . . . . . . . . . . . . . . .. . ...... 77

Neurotoxic Effects of Amoscanate, Rat G.J. KRINKE .. . . .. .... . ..... .

Neurotoxic Effects of 2-Chloroprocaine and Other Local Anesthetics, Rat

84

R. R. MYERS, M. W. KALICHMAN, and H. C. POWELL . . . . . . . 87

X Table of Contents

Systemic Degenerative Disorders of Primary Sensory Neurons in Rats Induced by 4-Hydroxyaminoquinoline 1-0xide Y. HAYASHI, M. TAKAHASHI, and T. HASEGAWA . . . . . . . . . 92

Inorganic Mercury Poisoning, Rat K.R.REUHL ............ . 98

Tellurium Poisoning, Rat K.R.REUHL ....... . . 101

Cadmium Poisoning, Rat K.R.REUHL .............................. 104

Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

Benign and Malignant Neoplasms, Meninges, Rat K. MITSUMORI, S. A. STEFANSKI, and R. R. MARON POT .. 108

Malignant Reticulosis, Rat R. H. GARMAN . . . . . . . . . .

Gliomas, Mouse K.T.MORGAN and R.H.ALISON

Lipoma, Brain, Mouse K.T.MORGAN and W.G.SHELDON .

Gliomas, Rat

.. . 117

.. 123

. 130

V.E. WALKER and J.A.SWENBERG ...... . .......... 134

Peripheral Nerve Sheath Tumors, Rat D. M. WALKER, V. E. WALKER, J. F. HARDISTY, K. T. MORGAN, and J.A.SWENBERG ....................... . . 143

Schwannomas (Induced) Cranial, Spinal, and Peripheral Nerves, Rat J.M.RICE and J.M. WARD ........... .

Malignant Melanotic Schwannomas Induced by 1,1-Dimethylhydrazine, European Hamster H. ERNST and U. MOHR .. . .... . ..... .

Cardiac Neurilemmoma, Rat

........ 154

. 160

J.M.RICEandJ.M.WARD ... . .................. 165

Infections ... .. .. . ... . .. .. ... .. .......... 170

Parvovirus Infection, Rat R.O.JACOBY ....... . .. 170

Encephalomyelitis, Theiler's Virus, Mouse R.O.JACOBY ................... . .. 175

Mouse Hepatitis Virus Infection, Brain, Mouse S.W.BARTHOLD .. .. .. ...... . ... . . .. 180

Lymphocytic Choriomeningitis, Mouse K. E. WRIGHT and M.J. BUCHMEIER ... .. . .......... 187

Table of Contents X I

Encephalitozoonosis, Central Nervous System, Rat, Mouse K. S . REGAN and J. A. SHADDUCK . . . . . . . . . . . . . 192

Toxoplasmosis, Nervous System, Mouse and H amster K.S.REGANandJ.A.SHADDUCK . . . . . . . . . . . . . . . . 197

Disorders: Inherited or of Unknown Etiology ... .... .. ... 203

Spontaneous Radiculoneuropathy, Aged Rats G. J. KRINKE ..... ... ... .... ... . .. . 203

Peripheral Neuropathy in the Mutant Syrian Hamster A. HIRANO and M.SHlNTAKU ... .... ... ... .. .... 208

Abberrant Synaptic Development in Mutant "Weaver" Mice A. HIRANOandM.SHI NTAKU ................. .. 215

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222

List of Contributors

Hisashi Aikawa, M.D. Chief, Neuroanatomy & Neuropathology Section National Institute of Neuroscience Tokyo, Japan

Roger H. Alison, BVSc, MRCVS National Toxicology Program Research Triangle Park, North Carolina, USA

Holger AJtenkirch, M.D. Associate Professor of Neurology Department of Neurology, Freie Universitat Berlin Berlin, Federal Republic of Germany

Stephen W. Barthold, D.V.M., Ph. D. Associate Professor, Yale University School of Medicine New Haven, Connecticut, USA

Michael J. Buchmeier, B.S., M.S., Ph. D. Associate Member, Department of Immunology Scripps Clinic and Research Foundation La Jolla, California, USA

Heinrich Ernst, D.V.M. Hannover Medical College Hannover, Federal Republic of Germany

Robert H. Garman, B.S., D.V.M. Senior Research Scientist, Carnegie-Mellon Institute of Research Bushy Run Research Center Export, Pennsylvania, USA

Susan M. Hall, B.Sc., Ph. D. Senior Lecturer, Department of Anatomy United Medical and Dental Schools London Bridge, England

Jerry F. Hardisty, D.V.M. Director, Experimental Pathology Laboratories Research Triangle Park, North Carolina, USA

Toshiaki Hasegawa, B.S. Senior Investigator, Shionogi Research Laboratories Osaka, Japan

Yuzo Hayashi, M. D., Ph. D. Chief, Department of Pathology National Institute of Hygienic Sciences Tokyo, Japan

XIV List of Contributors

Asao Hirano, M.D. Head, Division of Neuropathology, Montefiore Hospital & Medical Center Professor, Department of Pathology & Neuroscience, Albert Einstein College of Medicine New York, New York, USA

Fusahiro Ikuta, M.D. Professor and Chairman Department of Pathology, Niigata University Niigata, Japan

Robert O.Jacoby, D.V.M., Ph. D. Professor and Chairman Section of Comparative Medicine, Yale University New Haven, Connecticut, USA

Bernard S. Jortner, V. M.D. Professor of Pathology Virginia-Maryland Regional College of Veterinary Medicine Blacksburg, Virginia USA

Michael W. Kalichman, Ph. D. Assistant Professor of Anesthesiology, University of California San Diego, California, USA

Makoto Koga, D. M. Sc., M.D. Associate Professor of Neuropathology Neurological Institute, Faculty of Medicine, Kyushu University Fukuoka, Japan

Georg J . Krinke, MVDr Research Associate Department of Toxicological Pathology, CI BA-GEIGY AG Basel, Switzerland

Akihiko Maekawa, M. D., Ph. D. Chief, Department of Chemical Pathology National Institute of Hygienic Sciences Tokyo, Japan

Robert Maron pot, D.V.M., M.S., M.P. H. Head, Experimental Pathology National Toxicology Program Research Triangle Park, North Carolina, USA

Yasuhiko Matsuki, Ph. D. Chief, Pharmacokinetic Laboratory Hatano Research Institute, Food and Drug Safety Center Kanagawa, Japan

Kunitoshi Mitsumori, D.V. M., Ph. D. National Toxicology Program Research Triangle Park, North Carolina, USA

Ulrich Mohr, M.D. Professor of Experimental Pathology Hannover Medical College Hannover, Federal Republic of Germany

List of Contributors XV

Kevin T. Morgan, B. V. Sc., Ph. D., M. R. C. Path. Chemical Industry Institute of Toxicology Research Triangle Park, North Carolina, USA

Robert R. Myers, Ph. D. Associate Professor, Anesthesiology and Neurosciences School of Medicine, University of California La Jolla, California, USA

Henry C. Powell, M.D., B. Ch., M. R. C. Path. Professor of Pathology School of Medicine, University of California La Jolla, California, USA

Karen S. Regan, D.V.M. Teaching and Research Associate in Pathology College of Veterinary Medicine Urbana, Illinois, USA

Kenneth R. Reuhl, Ph. D. Associate Professor Department of Pharmacology & Toxicology School of Pharmacy, Rutgers University New Jersey, USA

Jerry M. Rice, Ph. D. Chief, Laboratory of Comparative Carcinogenesis National Institutes of Health, National Cancer Institute Frederick, Maryland, USA

Bernhard Ryffel, M.D. Assistant Professor, Pharmacology Division, SANDOZ Pratteln, Switzerland

Dr. Yuji Sato Department of Neuropathology, Kyushu University Fukuoka,Japan

John A. Shadduck, D.V.M., Ph. D. Professor and Head Department of Veterinary Pathobiology College of Veterinary Medicine Urbana, Illinois, USA

Winslow G. Sheldon, D.V.M. Pathology Associates, Inc. Jefferson, Arkansas, USA

Masayuki Shintaku, M.D. Assistant Professor Department of Pathology, Kansai Medical University, Japan Visiting Fellow, Division of Neuropathology Montefiore Medical Center Bronx, New York, New York, USA

Steven A. Stefanski, D.V.M., M.S. Staff Pathologist, National Toxicology Program-NIEHS Research Triangle Park, North Carolina, USA

XVI List of Contributors

Gisela Stoltenburg-Didinger, M.D. Associate Professor of Neuropathology Freie UniversiUit Berlin Berlin, Federal Republic of Germany

Kinuko Suzuki, M. D. Professor Department of Pathology University of North Carolina Chapel Hill, North Carolina, USA

James A.Swenberg, D.V.M., Ph.D. Head, Department of Biochemical Toxicology and Pathobiology Chemical Industry Institute of Toxicology Research Triangle Park, North Carolina, USA

Michihito Takahashi, M.D., Ph. D. Chief, Department of Pathology National Institute of Hygienic Sciences Tokyo, Japan

Jun Tateishi, D. M. Sc., M.D. Chairman, Department of Neuropathology Neurological Institute, Faculty of Medicine, Kyushu University Kyushu, Japan

Dale M. Walker, D.V.M. Staff Pathologist, Experimental Pathology Laboratories, Inc. Research Triangle Park, North Carolina, USA

Vernon E. Walker, D.V.M. Chemical Industry Institute of Toxicology Research Triangle, Park North Carolina, USA

Jerrold M. Ward, D.V.M., Ph. D. Chief, Tumor Pathology and Pathogenesis Section Laboratory ofComparative Carcinogenesis, National Cancer Institute Frederick, Maryland, USA

Kathryn E. Wright, B. A., M.A., M. Sc., Ph. D. Post-doctoral Research Fellow, Canadian Arthritis Society Scripps Clinic and Research Foundation La Jolla, California, USA

Yasuji Yoshida, M.D. Department of Neuropathology Brain Research Institute, Niigata University Niigata, Japan

Shinsuke Yoshimura, D.V. M. Hatano Research Institute, Food and Drug Safety Center Kanagawa, Japan