Preface

The concept of animal models dealt in this book discusses appropriate mechanistic models for several prevalent human diseases. Animal models are imperative for preclinical trials, disease pathway and pathological elucidation, new drug development, environmental test‐ ing, and vaccine construction. Against any odds, the use of animals (from primates to mur‐ ine), especially rat and mouse, seems indispensable in today's scientific world. The book presents reproducible experimental approach using animal models for the study of human diseases with measurable equivalence to that of humans. It also presents models of high hu‐ man predictive value. Despite current insights and promising technologies, no scientific method can at this time fully address the limitation(s) of using animal models as complete surrogates for humans. The organization of the book is unique and organic because it brings to the fore the implications, pros and cons, and choice of experimental animals in research design for scientists and clinicians. An important objective of the book is to provide a wider readership of scientist, clinicians, and ethicist. It also provides a multidisciplinary approach to modeling animals for the study of human diseases and on the basics in choosing animal models. The need to qualify and/or standardize animal models is evident at the least to spe‐ cifically and reproducibly produce a disease process or condition that in multiple important aspects corresponds to the human disease or condition of interest. The question of whether or not there should be a standardized or qualification model is one of the main current con‐ troversies in developing animal models for human diseases. This is also addressed in the chapter contributions.

Each chapter of this book further discuses new-generation model of animals for human dis‐ ease study. Chapter 1 is the introduction describing the major contributions of animal mod‐ els to modern medicine. The book therefore is divided into three (3) sections: the first section deals with diabetes and obesity in five (5) chapters. Chapters 2 and 3 "Animal Models of Diabetic Retinopathy" x-ray the suitability of available animal models (from chemically in‐ duced to transgenic) for therapeutic drug screening and further understanding of the molec‐ ular and cellular pathological processes involved in DR. The availability of a holistic animal model that reproduces the pathological progression of human DR is presented. Chapter 4 "Animal Models of Central Diabetes Insipidus: Oxytocin and Low-Sodium Diets as Comple‐ mentary Treatments" describes the animal model of hereditary human central diabetes in‐ sipidus (CDI); the authors asserted that the hydromineral characteristics of these animals do not seem to be fully comparable with an acquired CDI animal model such as transgenic rat TGR(ASrAOGEN)680, TGR(mREN2)27, etc.; additionally, the variations in the neurobiologi‐ cal system evidently predict individualized therapies desirable to improve the quality of life of the patients. Chapter 5 "Animal Models of Obesity: The Potential Role of Nonalcoholic Hepatic Steatosis" describes the mechanisms involved in the progression from NAFLD to

NASH, which are not yet clearly elucidated, as some models have shown unexpected out‐ comes such as severe malnutrition or the absence of obesity markers and IR after the use of minimal-change disease (MCD) therapies and drugs, respectively. Thus, the importance of evaluating different animal models of obesity is to induce the profile of NAFLD and NASH disease in humans, assessing their mechanisms of action. Chapter 6 "Rodent Models of Met‐ abolic Disorders: Obesity and Diabetes" emphasizes various metabolic disorders that are not only congenital but also can be acquired or coexistent with both types. The chapter describes fully transgenic animal models available, focusing on global emerging pathologies, obesity, diabetes, and metabolic syndrome. The second section with five (5) chapters discuses in‐ flammatory and viral infections. Chapter 7 "Animal Models of Double Incontinence: Fecal and Urinary" considers the use of animals as models to understand pathogenesis, diagnosis, and management of double incontinence (DI), a complex disease of urinary and anal abnor‐ mality. The chapter points to animal models as an imperative to train surgeons for perineal tear repair surgery. Chapter 8 "Relevance of the CDE and DDC Mouse Models to Study Ductular Reaction in Chronic Human Liver Diseases" discusses ductal reaction (DR) ob‐ served in chronic liver disorders important in hepatic cell restoration, fibrosis, or carcino‐ genesis. In humans, observational studies are available, but experimental manipulations and lineage tracing are impossible. The authors thus presented and compared two (2) animal models from a practical point of view describing the pathophysiological mechanisms at play in each model and their experimental procedures. Chapter 9 "Experimental Animal Models of HIV/AIDS for Vaccine Trials" details current animal models for invasive investigation of HIV disease mainly in preclinical evaluation of drugs and vaccines and success achieved. A comparison of nonhuman primate and murine model immunogenetics in response to re‐ combinant viruses as options of animal models available for research was tabulated. Chap‐ ter 10 "Animal Inhalation Models to Investigate Modulation of Inflammatory Bowel Diseases" examines the suitability of animal inhalation/smoke exposure models for assess‐ ing the contrary effects of cigarette smoke (CS) on ulcerative colitis (UC) and Crohn's dis‐ ease (CD). It crystallizes various technical inhalation approaches, in the context of mouse disease models of IBD. Chapter 11 "The Use of Animal Models in the Study of Colitis" presents the current concept on animal models of inflammatory bowel diseases, describing genetically modified, chemical induction, cell transfer, and spontaneous inflammation mod‐ els. These models are crucial for the understanding of inflammatory bowel diseases, devel‐ opment of alternative treatments, and more effective therapeutic agents, thus contributing to the control of the disease. The last section with six (6) chapters deals with stress, neurology, and regeneration. Chapter 12 "Evaluation of Animal Models Suitable for Hair Research and Regeneration" evaluates animal models for hair regeneration (alopecia), a frequent dermato‐ logical disease with limited treatment options, as well as presents current experimental data from suitable animal model. Chapter 13 "Animal Models of Rheumatoid Arthritis" focuses on the most common in vivo models used for the study of RA, including those related with genetic, immunological, hormonal, and environmental interactions. The chapter considers the CIA model to be the most successful in generating arthritis using type II collagen and adjuvants and evaluating therapeutic compounds both intra-articularly and systemically. Chapter 14 "Animal Models for Chronic Stress-Induced Oxidative Stress in the Spleen: Role of Exercise and Catecholaminergic System" explains an experimental approach including research methodology and evaluated results for combined animal model of chronic social isolation and long-term daily treadmill running in rats and "cross-stressor adaptation hy‐ pothesis." The model seems to be a highly predictive animal model for research on the ther‐

apeutic role of exercise in human disease caused by chronic stress. Chapter 15 "Studying Side Effects of Tyrosine Kinase Inhibitors in a Juvenile Rat Model with Focus on Skeletal Remodeling" sorts out important and effective treatment for chronic myeloid leukemia (CML) targeting the causative oncogenic TK BCR-ABL1 using tyrosine kinase inhibitor (TKI) imatinib in animal model. As TKI treatment might be necessary for a lifetime, long-term side effects exerted on bone and other developing organs in children are of major concern and are not yet studied systematically; the chapter described a new juvenile rat model to face this challenge and presented extensive experimental evidence. Chapter 16 "Animal Models of Fetal Medicine and Obstetrics" demonstrates the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia, and gestational diabetes. These conditions differ in relation to animal characteristics (size, number of fetuses, placenta barrier type, etc.) and do not exactly mirror the human condi‐ tion; different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep, and pigs), however, are available as described with respect to advantages and limitations for careful choice of experimental model. Chapter 17 "Animal Model of Parkinson Disease: Neuroinflammation and Apoptosis in the 6-Hydroxydopamine-Induced Model" elucidates the animal-to-human replication of Parkinson disease (PD)-induced 6-hydroxydopamine (6-

Sincere appreciation is given to contributors who have extended their full cooperation with the publisher IntechOpen for presenting their expert contributions contained in the book.

**Ibeh Bartholomew, PhD**

Abuja, Nigeria

Preface XI

Medical Biotechnology Department

National Biotechnology Development Agency

OHDA) model, which will aid in PD therapeutic design.

apeutic role of exercise in human disease caused by chronic stress. Chapter 15 "Studying Side Effects of Tyrosine Kinase Inhibitors in a Juvenile Rat Model with Focus on Skeletal Remodeling" sorts out important and effective treatment for chronic myeloid leukemia (CML) targeting the causative oncogenic TK BCR-ABL1 using tyrosine kinase inhibitor (TKI) imatinib in animal model. As TKI treatment might be necessary for a lifetime, long-term side effects exerted on bone and other developing organs in children are of major concern and are not yet studied systematically; the chapter described a new juvenile rat model to face this challenge and presented extensive experimental evidence. Chapter 16 "Animal Models of Fetal Medicine and Obstetrics" demonstrates the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia, and gestational diabetes. These conditions differ in relation to animal characteristics (size, number of fetuses, placenta barrier type, etc.) and do not exactly mirror the human condi‐ tion; different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep, and pigs), however, are available as described with respect to advantages and limitations for careful choice of experimental model. Chapter 17 "Animal Model of Parkinson Disease: Neuroinflammation and Apoptosis in the 6-Hydroxydopamine-Induced Model" elucidates the animal-to-human replication of Parkinson disease (PD)-induced 6-hydroxydopamine (6- OHDA) model, which will aid in PD therapeutic design.

NASH, which are not yet clearly elucidated, as some models have shown unexpected out‐ comes such as severe malnutrition or the absence of obesity markers and IR after the use of minimal-change disease (MCD) therapies and drugs, respectively. Thus, the importance of evaluating different animal models of obesity is to induce the profile of NAFLD and NASH disease in humans, assessing their mechanisms of action. Chapter 6 "Rodent Models of Met‐ abolic Disorders: Obesity and Diabetes" emphasizes various metabolic disorders that are not only congenital but also can be acquired or coexistent with both types. The chapter describes fully transgenic animal models available, focusing on global emerging pathologies, obesity, diabetes, and metabolic syndrome. The second section with five (5) chapters discuses in‐ flammatory and viral infections. Chapter 7 "Animal Models of Double Incontinence: Fecal and Urinary" considers the use of animals as models to understand pathogenesis, diagnosis, and management of double incontinence (DI), a complex disease of urinary and anal abnor‐ mality. The chapter points to animal models as an imperative to train surgeons for perineal tear repair surgery. Chapter 8 "Relevance of the CDE and DDC Mouse Models to Study Ductular Reaction in Chronic Human Liver Diseases" discusses ductal reaction (DR) ob‐ served in chronic liver disorders important in hepatic cell restoration, fibrosis, or carcino‐ genesis. In humans, observational studies are available, but experimental manipulations and lineage tracing are impossible. The authors thus presented and compared two (2) animal models from a practical point of view describing the pathophysiological mechanisms at play in each model and their experimental procedures. Chapter 9 "Experimental Animal Models of HIV/AIDS for Vaccine Trials" details current animal models for invasive investigation of HIV disease mainly in preclinical evaluation of drugs and vaccines and success achieved. A comparison of nonhuman primate and murine model immunogenetics in response to re‐ combinant viruses as options of animal models available for research was tabulated. Chap‐ ter 10 "Animal Inhalation Models to Investigate Modulation of Inflammatory Bowel Diseases" examines the suitability of animal inhalation/smoke exposure models for assess‐ ing the contrary effects of cigarette smoke (CS) on ulcerative colitis (UC) and Crohn's dis‐ ease (CD). It crystallizes various technical inhalation approaches, in the context of mouse disease models of IBD. Chapter 11 "The Use of Animal Models in the Study of Colitis" presents the current concept on animal models of inflammatory bowel diseases, describing genetically modified, chemical induction, cell transfer, and spontaneous inflammation mod‐ els. These models are crucial for the understanding of inflammatory bowel diseases, devel‐ opment of alternative treatments, and more effective therapeutic agents, thus contributing to the control of the disease. The last section with six (6) chapters deals with stress, neurology, and regeneration. Chapter 12 "Evaluation of Animal Models Suitable for Hair Research and Regeneration" evaluates animal models for hair regeneration (alopecia), a frequent dermato‐ logical disease with limited treatment options, as well as presents current experimental data from suitable animal model. Chapter 13 "Animal Models of Rheumatoid Arthritis" focuses on the most common in vivo models used for the study of RA, including those related with genetic, immunological, hormonal, and environmental interactions. The chapter considers the CIA model to be the most successful in generating arthritis using type II collagen and adjuvants and evaluating therapeutic compounds both intra-articularly and systemically. Chapter 14 "Animal Models for Chronic Stress-Induced Oxidative Stress in the Spleen: Role of Exercise and Catecholaminergic System" explains an experimental approach including research methodology and evaluated results for combined animal model of chronic social isolation and long-term daily treadmill running in rats and "cross-stressor adaptation hy‐ pothesis." The model seems to be a highly predictive animal model for research on the ther‐

X Preface

Sincere appreciation is given to contributors who have extended their full cooperation with the publisher IntechOpen for presenting their expert contributions contained in the book.

> **Ibeh Bartholomew, PhD** Medical Biotechnology Department National Biotechnology Development Agency Abuja, Nigeria

**Section 1**

**Introduction**

**Section 1**
