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Neuromethods 104 Jerome Y. Yager Editor Animal Models of Neuro- developmental Disorders N EUROMETHODS Series Editor Wolfgang Walz University of Saskatchewan Saskatoon, SK, Canada For further volumes: h ttp://www.springer.com/series/7657 Animal Models of Neurodevelopmental Disorders Edited by Jerome Y. Yager Division of Pediatric Neurology, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada Editor Jerome Y . Yager Division of Pediatric Neurology Department of Pediatrics University of Alberta Edmonton, AB, Canada ISSN 0893-2336 ISSN 1940-6045 (electronic) Neuromethods ISBN 978-1-4939-2708-1 ISBN 978-1-4939-2709-8 (eBook) DOI 10.1007/978-1-4939-2709-8 Library of Congress Control Number: 2015944115 Springer New York Heidelberg Dordrecht London © Springer Science+Business Media New York 2 015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Humana Press is a brand of Springer Springer Science+Business Media LLC New York is part of Springer Science+Business Media (www.springer.com) Series P reface Experimental life sciences have two basic foundations: concepts and tools. The N euromethods series focuses on the tools and techniques unique to the investigation of the nervous system and excitable cells. It will not, however, shortchange the concept side of things as care has been taken to integrate these tools within the context of the concepts and questions under investigation. In this way, the series is unique in that it not only collects protocols but also includes theoretical background information and critiques which led to the methods and their development. Thus it gives the reader a better understanding of the origin of the techniques and their potential future development. The N euromethods publishing program strikes a balance between recent and exciting developments like those concerning new animal models of disease, imaging, in vivo methods, and more established techniques, includ- ing, for example, immunocytochemistry and electrophysiological technologies. New trainees in neurosciences still need a sound footing in these older methods in order to apply a critical approach to their results. Under the guidance of its founders, Alan Boulton and Glen Baker, the Neuromethods series has been a success since its fi rst volume published through Humana Press in 1985. The series continues to fl ourish through many changes over the years. It is now published under the umbrella of Springer Protocols. While methods involving brain research have changed a lot since the series started, the publishing environment and technology have changed even more radically. Neuromethods has the distinct layout and style of the Springer Protocols program, designed specifi cally for readability and ease of reference in a laboratory setting. The careful application of methods is potentially the most important step in the process of scientifi c inquiry. In the past, new methodologies led the way in developing new disciplines in the biological and medical sciences. For example, Physiology emerged out of Anatomy in the nineteenth century by harnessing new methods based on the newly discov- ered phenomenon of electricity. Nowadays, the relationships between disciplines and methods are more complex. Methods are now widely shared between disciplines and research areas. New developments in electronic publishing make it possible for scientists that encounter new methods to quickly fi nd sources of information electronically. The design of individual volumes and chapters in this series takes this new access technology into account. Springer Protocols makes it possible to download single protocols separately. In addition, Springer makes its print-on-demand technology available globally. A print copy can therefore be acquired quickly and for a competitive price anywhere in the world. Wolfgang W alz v Prefa ce The defi nition of the Developmental Disabilities has evolved over the last number of years, and thankfully as a result, encompasses a broad range of individuals with both cognitive and motor impairment. One recent defi nition put forward is that of a “disability manifested before a person reaches maturity and is attributable to mental retardation or related conditions and includes cerebral palsy, epilepsy, autism, or other neurological condition, when such conditions result in the impairment of general intellectual functioning or adaptive behavior.” Of course, many jurisdictions and governmental ministries have defi nitions which vary and are at times exclusive to some disabilities, which the health and scientifi c fi eld would include. Nonetheless, as it relates to the research community, we recognize this terminology as encompassing a very wide range of diseases that span a broad spectrum of brain maturation and include numerous etiologies, at times resulting in similar and overlap- ping phenotypes. Because of this, identifying animal models which refl ect and are inclusive to this host of diseases is a daunting challenge. As a goal to success, at least as this area of investigation relates to health, the animal model must be able to provide a refl ection of the human condition, both short and long term, the ability to investigate mechanisms of injury and outcome, biomarkers of disease, and a portal by which therapeutic interventions for the long-term benefi t of the individual may be tested. Herein lies a particular challenge, as many of the disabilities discussed in this text relate to injuries evolving during pregnancy, have both genetic and environmental components infl uencing their outcome, and in the human population, often require years of follow-up to determine effectiveness. The lack of translatability of many animal models, from a therapeutic perspective, has signifi cantly chal- lenged researchers to seek novel in vivo models of disease that better refl ect the human condition and will allow for outcomes in therapy that will transfer to the human. As diseases become better understood, the healthcare community and the applied basic sciences have identifi ed the need to become person- and certainly disease-specifi c. Undoubtedly in the “adult” world, there have been numerous potential therapies in animal research that have not been successfully translated to the human, as determined by clinical trials. One of the explanations, and probably just one, is that our animal models seek to identify specifi c variables, which cannot then be broadly applied. Hence, both the clinical and applied animal research communities are becoming more specifi c in their models, and so they should be for their application to the human phenotype. One of the more successful translations has been the use of hypothermia as a rescue therapy for perinatal asphyxia. Hypothermia has been successful in several models of hypoxic-ischemic brain injury, across several species, and in clinical trials in humans. This is partially due to the fact that it was recognized as a specifi c therapy for specifi c circumstances, that being term and near-term acute neonatal encephalopathy caused by hypoxia-ischemia. While it was not the intent of this manual to be all inclusive, we have accumulated a host of authors well recognized in their fi elds of expertise, with all contributors involved in the investigation of the causes, outcomes, treatment, and prevention of the developmental disabilities. We have further attempted to provide a spectrum of models that is refl ective of the various species that can be utilized in experimentation on these disorders across a broad vii viii Preface range of the disabilities. This text is meant to introduce and entice those interested in better understanding and treating the developmental disorders, to animal models that best refl ect that spectrum of disability in the human. Certainly, as a clinician-scientist who has worked in the fi eld for the last two decades, the area of investigation has grown substantially. But what is just as clear is that no one animal model will suffi ce to provide us with all of the answers. And as we move increasingly to patient-specifi c forms of therapy, the need for animal models that encompass the specifi cs of the underlying mechanisms, refl ect the phenotypic expression, and take into account environmental and genetic infl uences, both ante nataly and post nataly, will be required. My deepest thanks go to Dr. Robert C. Vannucci, who introduced me to the world of perinatal brain injury and the developmental disabilities, to the role of animal models in the science of investigation, and for allowing me the opportunity to learn from one of the pio- neers of modern perinatal neurology. I also wish to thank each of the authors in this text for their patience and their tremendous contributions to the fi eld of brain injury in the newborn, its understanding, and our ability to move forward in diminishing the burden of the developmental disabilities. And, of course to the patients I see every day with cerebral palsy and other developmental disabilities, from whom I learn far more than I could ever contribute. Edmonton, AB, Canada Jerome Y. Y ager Contents Series Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 1 U nilateral Common Carotid Artery Ligation as a Model of Perinatal Asphyxia: The Original Rice–Vannucci Model. . . . . . . . . . . . . . . . 1 Antoinette N guyen , E dward A . Armstrong , and Jerome Y . Yager 2 B ilateral Uterine Artery Ligation (BUAL): Placental Insufficiency Causing Fetal Growth Restriction and Cerebral Palsy . . . . . . . . . . . . . . . . . . . 15 Jennifer Corrigan , Edward A . A rmstrong , S tuart Faulkner , Crystal A. Ruff , M ichael Fehlings , and Jerome Y . Yager 3 Perinatal Intracerebral Hemorrhage Model and Developmental Disability. . . . 29 Janani K assiri and Marc D el Bigio 4 P reterm Rabbit Model of Glycerol-Induced Intraventricular Hemorrhage. . . . 45 P raveen B allabh 5 M odels of Perinatal Brain Injury in Premature and Term Newborns Resulting from Gestational Inflammation Due to Inactivated Group B Streptococcus (GBS), or Lipopolysaccharide (LPS) from E. coli and/or Immediately Postnatal Hypoxia-Ischemia (HI). . . . . . . . . 55 Julie B ergeron , Marie-Julie Allard , Clémence Guiraut , Mathilde Chevin , A lexandre S avard , Djordje G rbic , M arie-Elsa B rochu , and Guillaume S ébire 6 Fetal Brain Activity in the Sheep Model with Intrauterine Hypoxia . . . . . . . . . 6 5 Bryan S. Richardson and B rad Matushewski 7 S tudies of Perinatal Asphyxial Brain Injury in the Fetal Sheep . . . . . . . . . . . . . 8 5 Paul P. Drury , Laura B ennet , L indsea C. B ooth , J oanne O. Davidson , Guido W assink , and Alistair J an G unn 8 The Sheep as a Model of Brain Injury in the Premature Infant. . . . . . . . . . . . . 107 Stephen A. Back , Art Riddle , and A. Roger Hohimer 9 T he Rabbit as a Model of Cerebral Palsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Kehuan Luo , Jessica Baker , Matthew Derrick , and Sidhartha T an 10 A Newborn Piglet Survival Model of Post-hemorrhagic Ventricular Dilatation (PHVD). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 Kristian A quilina and Marianne T horesen 11 Physiologic Aspects of the Piglet as a Model of Neonatal Hypoxia and Reoxygenation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Richdeep S . G ill , David L . B igam , and Po-Yin Cheung 12 T he Newborn Pig Global Hypoxic-Ischemic Model of Perinatal Brain and Organ Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 71 Elavazhagan Chakkarapani and Marianne Thoresen ix