This book offers pathologists, toxicologists, other medical professionals, and students an introduction to the discipline and techniques of neuropathology including chemical and environmental, biological, medical, and regulatory details important for performing an analysis of toxicant-induced neurodiseases. In addition to a section on fundamentals, the book provides detailed coverage of current practices (bioassays, molecular analysis, and nervous system pathology) and practical aspects (data interpretation, regulatory considerations, and tips for preparing reports).
BRAD BOLON, DVM, MS, PhD, Diplomate ACVP, Diplomate ABT, Fellow ATS, Fellow IATP, has spent over twenty years as a practitioner and teacher of toxicologic neuropathology. He is the founder of GEMpath, Inc., an experimental pathology consultancy specializing in drug discovery research. MARK T. BUTT, DVM, Diplomate ACVP, is the founder of Tox Path Specialists, LLC, a company that provides neuropathology and histology support to pharmaceutical and biotechnology firms developing novel therapies that target nervous system diseases. He has over twenty years' experience providing neuropathology support and has evaluated over four hundred studies supporting regulatory submissions for neuroactive compounds.
Editors Preface. Forward. Acknowledgments. Part I. Fundamentals of Neurobiology. Chapter 1. Fundamentals of Toxicologic Neuropathology: An Introduction. Chapter 2. Functional Neuroanatomy. Chapter 3. Atlas of Comparative Neuroanatomy. Chapter 4. Principles of Comparative and Correlative Neurodevelopment, and their Implications for Developmental Neurotoxicity. Chapter 5. Localizing Neuropathologic Lesions Using Neurologic Findings. Chapter 6. Behavioral Model Systems for Evaluating Neuropathology. Chapter 7. Cognitive Assessments in Non-Human Primates. Chapter 8. The Impact of Aging on Brain Structure and Function in Rodents and Canines. Chapter 9. Fundamentals of Neurotoxicity Detection. Part 2. Toxicologic Neuropathology: Methodology. Chapter 10. Practical Neuropathology of the Rat and Other Species. Chapter 11. The Fluoro-Jade Dyes: Novel, Sensitive, and Reliable Fluorochromes for the Histochemical Localization of Degenerating Neurons. Chapter 12. Histologic Markers of Neurotoxicity (Nonfluorenscence). Chapter 13. Common Histologic Artifacts in Nervous System Tissues. Chapter 14. High-Definition Microscopic Analysis of the Nervous System. Chapter 15. Stereological Solutions for Common Quantitative Endpoints in Neurotoxicity. Chapter 16. Anatomy and Processing of Peripheral Nerve Tissues. Chapter 17. Pathology Methods in Non-clinical Neurotoxicity Studies: Evaluation of Muscle. Chapter 18. In Vivo Imaging Applications for the Nervous System in Animal Models. Chapter 19. Cerebrospinal Fluid Analysis in Toxicologic Neuropathology. Chapter 20. Molecular Techniques in Toxicologic Neuropathology. Part 3. Toxicologic Neuropathology: Current Practices. Chapter 21. Evaluation of the Adult Nervous System in Preclinical Studies. Chapter 22. Pathology Methods in Non-clinical Neurotoxicity Studies: Developing Central Nervous System. Chapter 23. Neuropathology Analysis of the Peripheral Nervous System. Chapter 24. Toxicologic Pathology of the Retina and Optic Nerve. Chapter 25. Toxicologic Neurpathology of the Ear. Chapter 26. Neurpathology of the Olfactory System. Part 4. Applied Toxicologic Neuropathology. Chapter 27. Spinal Delivery and Assessment of Drug Safety. Chapter 28. Diagnostic Neuropathology. Chapter 29. Toxicologic Neuropathology in Medical Practice. Chapter 30. Toxiciologic Neuropathology in Veterinary Practice. Chapter 31. Regulatory Considerations in Toxicologic Neuropathology. Chapter 32. The Neuropathology Report and the Neuropathology Peer Review Report. Chapter 33. Preparation of Personnel for Neuropathology Assessment. Chapter 34. Regulatory Guide to the Histopathologic Assessment of Neurotoxicity Studies. Chapter 35. Toxicologic Neuropathology: The Next Two Decades. Appendices. Ready References of Neurobiology Knowledge. Appendix 1. Neural Cell Markers of Potential Utility for Toxicologic Neuropathology Applications. Appendix 2. Neuroanatomic Atlases for Toxicologic Neuropathology Studies. Appendix 3. Text-Based Basic Neurobiology References for Toxicologic Neuropathologists. Appendix 4. Web-Based Neurobiology References for Toxicologic Neuropathogists. Appendix 5. Toxicologic Neuropathology References for Nervous System Targets. Appendix 6. Comparative and Correlative Neurobiological Parameters Related to Neuropathology Assessment. Appendix 7. Comparison of Central Nervous System Proportions Between Humans and Rats. Appendix 8. Chemical Composition of Central Nervous System Tissues and Fluids.