Rodent Models of Stroke

351 Pages·2016·9.276 MB·English

by  Ulrich Dirnagl

Neuromethods 120
Ulrich Dirnagl Editor
Rodent
Models
of Stroke
Second Edition
N
EUROMETHODS
Series Editor
Wolfgang Walz
University of Saskatchewan
Saskatoon , SK , Canada
For further volumes:
h ttp://www.springer.com/series/7657

Rodent Models of Stroke
Second Edition
Edited by
Ulrich Dirnagl
Department of Experimental Neurology and Center for Stroke Research Berlin (CSB),
Charité-Universitätsmedizin Berlin, Berlin, Germany;
German Center for Neurodegenerative Diseases (DZNE) and German Center
for Cardiovascular Diseases (DZHK), Berlin, Germany;
Excellence Cluster NeuroCure, Berlin, Germany;
Berlin Institute of Health, Berlin, Germany
Editor
Ulrich D irnagl
Department of Experimental Neurology
and Center for Stroke Research Berlin (CSB)
Charité-Universitätsmedizin Berlin, Berlin, Germany
German Center for Neurodegenerative Diseases (DZNE)
and German Center for Cardiovascular Diseases (DZHK)
Berlin, Germany
Excellence Cluster NeuroCure, Berlin, G ermany
Berlin Institute of Health, Berlin, Germany
Videos can also be accessed at h ttp://link.springer.com/book/10.1007/978-1-4939-5620-3
ISSN 0893-2336 ISSN 1940-6045 (electronic)
Neuromethods
ISBN 978-1-4939-5618-0 ISBN 978-1-4939-5620-3 (eBook)
DOI 10.1007/978-1-4939-5620-3
Library of Congress Control Number: 2016951315
© Springer Science+Business Media New York 2 016
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
This Humana Press imprint is published by Springer Nature
The registered company is Springer Science+Business Media LLC New York
Preface to t he Series
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 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 N euromethods
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. N euromethods has the distinct layout and style of the Springer Protocols pro-
gram, 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 Walz
v

Prefa ce
Despite major advances in prevention, acute treatment, and rehabilitation, stroke remains a
major burden on patients, relatives, and economies. The role and potential benefi ts of
experimental models of stroke (i.e., focal cerebral ischemia) in rodents have been recently
debated. Critics argue that numerous treatment strategies have been tested successfully in
models only to be proven dismal failures when tested in controlled clinical trials.
When methods of systematic review and meta-analysis are applied, however, it turns out
that experimental models actually did faithfully predict the negative outcomes of clinical
trials. For example, thrombolysis with tissue plasminogen activator (t-PA), the only clini-
cally effective pharmacological treatment of acute ischemic stroke, was fi rst demonstrated
and evaluated in an experimental model of stroke. Many other examples document the
positive prediction of rodent stroke models even beyond the brain, such as changes in the
immune system and susceptibility to infection after stroke. These were fi rst described and
can be faithfully modeled in rodents.
Beyond its role in investigating pathomechanisms of stroke and in preclinical testing for
the effi cacy of novel diagnostic and treatment strategies, rodent stroke is often used as a
“model” for how the brain reacts to neurological injury (damage, protection, repair), with
implications for many other neurological disorders such as brain and spinal cord injury,
epilepsy, and even multiple sclerosis. Concepts such as “neuroprotection,” “precondition-
ing,” and “ischemic penumbra” are largely the result of experimental stroke research.
Nevertheless, the issue of the relevance of experimental stroke research, in particular in
rodents, to human disease has to be taken seriously. A number of problems have been iden-
tifi ed which are prevalent in this research fi eld and impact on its predictiveness. These
include low statistical power, defi ciencies in experimental design, analysis, and reporting, as
well as publication bias, just to name a few. In addition, the validity of experimental stroke
research is affected when the effects of age, gender, and comorbidities are ignored in mod-
eling of stroke.
The fi rst edition of this volume was well received by the stroke research community. In
this second edition, our international consortium of authors updated and expanded their
comprehensive, critical, and very application-oriented approach to the toolbox of rodent
models of stroke. From choosing the model and outcome measures, designing the experi-
ment, and conducting and analyzing it to reporting it in a scientifi c publication, we are
offering food for thought as well as practical advice. This book is the result of long-standing
cooperation of many of the authors, not only scientifi c but also in teaching animal models
of stroke and good scientifi c practice to students and researchers. It is also the result of an
intense discussion of issues of validity and quality and its control. For more than 15 years,
several of the authors have been organizing the international course “Methods in Cerebral
Ischemia Research,” and many are jointly organizing training and dissemination of practical
knowledge in European Community-funded initiatives such as the European Stroke
Network or Multi-PART (Multicentre Preclinical Animal Research Team), as well as in the
Center for Stroke Research in Berlin. The structure and content of the book refl ect both
the authors’ long-standing expertise in experimental and clinical stroke research and their
roles in training the scientifi c community in the tools of the trade.
vii
viii Preface
We hope that this updated second edition will help its readers understand the limita-
tions and the opportunities of modeling stroke in rodents and enable them to conduct
experiments which will not only improve our understanding of the pathophysiology of this
devastating disorder but also serve as the basis for developing highly effective treatment.
Berlin, Germany U lrich Dirnagl
Contents
Preface to the Series. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x i
1 F rom Bedside to Bench: How Clinical Reality Should Instruct
Stroke Modeling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Dirk M . Hermann and Thorsten R. Doeppner
2 How to Avoid Bumping into the Translational Roadblock. . . . . . . . . . . . . . . . 7
Malcolm R . Macleod and Emily S ena
3 M odeling Focal Cerebral Ischemia in Rodents: Introduction and Overview. . . 1 9
Vincent Prinz and Matthias Endres
4 F ocal Cerebral Ischemia in the Mouse and Rat by Intraluminal Suture. . . . . . . 3 1
Ludmila Belayev , Matthias Endres , and Vincent Prinz
5 Focal Ischemia Models: Middle Cerebral Artery Occlusion Induced
by Electrocoagulation, Occluding Devices, and Endothelin-1 . . . . . . . . . . . . . 4 5
I. Mhairi M acrae
6 M ouse Model of in situ Thromboembolic Stroke and Reperfusion . . . . . . . . . 5 9
Orset Cyrille , Le Béhot A udrey , Bonnet A nne-Laure , M aysami S amaneh ,
and Vivien Denis
7 P hotochemical Models of Focal Brain Ischemia. . . . . . . . . . . . . . . . . . . . . . . . 6 9
Anja Urbach and Otto W . W itte
8 H ousing in an Enriched Environment: A Tool to Study Functional
Recovery After Experimental Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Karsten Ruscher and Tadeusz Wieloch
9 M odeling Risk Factors and Confounding Effects in Stroke . . . . . . . . . . . . . . . 9 3
Barry McColl , David Howells , Nancy R othwell , and Adam Denes
10 Effect of Anesthesia in Stroke Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 23
Richard J . Traystman
11 N oninvasive Brain Imaging in Small Animal Stroke Models: MRI, PET,
and SPECT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Abraham Martín , Pedro Ramos-Cabrer , and Anna M. Planas
12 N oninvasive Optical Imaging in Rodent Models of Stroke. . . . . . . . . . . . . . . . 1 87
Markus Vaas and Jan K lohs
13 B ehavioral Testing in Rodent Models of Stroke, Part I . . . . . . . . . . . . . . . . . . 1 99
René B ernard , M ustafa B alkaya , and André R ex
14 Behavioral Testing in Rodent Models of Stroke, Part II. . . . . . . . . . . . . . . . . . 2 25
Gerlinde A.S. M etz
ix