Animal Models of Neurodevelopmental Disorders

283 Pages·2015·10.063 MB·English

by  Jerome Y. Yager

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 ani-
mal 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 disci-
plines 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 meth-
ods 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 there-
fore 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 condi-
tions 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 condi-
tion, both short and long term, the ability to investigate mechanisms of injury and out-
come, 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 develop-
mental 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