Table Of ContentMethods in
Molecular Biology 982
Pietro Ghezzi
Anthony Cerami
Editors
Tissue-Protective
Cytokines
Methods and Protocols
M M B ™
ETHODS IN OLECULAR IOLOGY
Series Editor
John M. Walker
School of Life Sciences
University of Hertfordshire
Hat fi eld, Hertfordshire, AL10 9AB, UK
For further volumes:
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Tissue-Protective Cytokines
Methods and Protocols
Edited by
Pietro Ghezzi
Brighton and Sussex Medical School, Falmer, UK
Anthony Cerami
Leiden University Medical Center, Leiden, The Netherlands
Editors
Pietro Ghezzi Anthony Cerami
Brighton and Sussex Medical School Leiden University Medical Center
Falmer, UK Leiden, The Netherlands
ISSN 1064-3745 ISSN 1940-6029 (electronic)
ISBN 978-1-62703-307-7 ISBN 978-1-62703-308-4 (eBook)
DOI 10.1007/978-1-62703-308-4
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013932704
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Preface
In 2004, Pietro Ghezzi asked me to write a short introductory chapter for a book on TNF
he was putting together for this very same series. The focus of what I wrote then was on
TNF as an infl ammatory agent. In fact, our fi nding, in the 1980s, that cachexia associated
with in fl ammatory and infectious diseases was due to TNF opened the way to the develop-
ment of anti-TNF drugs that are now standard treatment for chronic infl ammatory
disease.
Now, I am asked again to write about the continuation of this saga. In 1998, with Mike
Brines and Carla Hand, I started investigating why patients who receive EPO feel well soon
after the fi rst treatment. That led to the discovery, published in 2000, that systemically
administered EPO is neuroprotective in animal models of ischemic and traumatic brain
injury. That paper opened the fi eld of the neuroprotective action of EPO. The protective
action of EPO was soon demonstrated in other tissues, hence the use of the term “tissue-
protective cytokine” (1). As in the case of TNF, we had to fi ght the commonplace that EPO
has only erythropoietic actions, that its receptor is present only in erythroid progenitor
cells, and that EPO is produced only by the kidney (2).
As in the case of TNF, originally identifi ed for its antitumor activities, we had to work
against the common belief that EPO is solely an erythropoietic cytokine acting solely on
erythroid progenitors. Several investigators also documented the expression of EPO in the
central nervous system and other tissues, against the common belief that only the kidney
and the foetal liver produce EPO.
From the perspective of pharmacological use, the erythropoietic action of EPO, by
increasing the haematocrit and activating platelets, has some undesired side effects as a tis-
sue-protectant, and this led to the development of novel non-erythropoietic EPO-derived
tissue-protective molecules some of which are described here.
I believe that tissue-protection will be a new fi eld of interest of cytokine biology, both
in discovering novel actions of known cytokines and in developing new drugs. In this con-
text, this book is a valuable collection of methodological papers that describe in detail the
key models that have been used to characterize the tissue-protective actions of EPO and
derivatives and will, hopefully, be of use in the discovery of new tissue-protective
molecules.
Leiden, The Netherlands Anthony Cerami
References
1. Cerami A (2011) The value of failure: the discovery of TNF and its natural inhibitor erythropoietin.
J Intern Med 269(1):8–15
2. Ghezzi P, Bernaudin M, Bianchi R, Blomgren K, Brines M, Campana W, Cavaletti G, Cerami A,
Chopp M, Coleman T, Digicaylioglu M, Ehrenreich H, Erbayraktar S, Erbayraktar Z, Gassmann M,
Genc S, Gokmen N, Grasso G, Juul S, Lipton SA, Hand CC, Latini R, Lauria G, Leist M, Newton
SS, Petit E, Probert L, Sfacteria A, Siren AL, Talan M, Thiemermann C, Westenbrink D, Yaqoob M,
Zhu C (2010) Erythropoietin: not just about erythropoiesis. Lancet 375(9732):2142
v
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
1 Erythropoietin and Engineered Innate Repair Activators. . . . . . . . . . . . . . . . 1
Michael Brines and Anthony Cerami
2 Epo and Non-hematopoietic Cells: What Do We Know?. . . . . . . . . . . . . . . . 13
Omolara O. Ogunshola and Anna Yu. Bogdanova
3 Tissue-Protective Cytokines: Structure and Evolution . . . . . . . . . . . . . . . . . . 43
Pietro Ghezzi and Darrell Conklin
4 The Regenerative Activity of Interleukin-6 . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Eithan Galun and Stefan Rose-John
5 Brain Ischemic Injury in Rodents: The Protective Effect of EPO. . . . . . . . . . 79
Annelise Letourneur, Edwige Petit, Simon Roussel, Omar Touzani,
and Myriam Bernaudin
6 Experimental Traumatic Spinal Cord Injury . . . . . . . . . . . . . . . . . . . . . . . . . 103
Zübeyde Erbayraktar, Necati Gökmen,
Osman Yılmaz, and Serhat Erbayraktar
7 Erythropoietin as a Neuroprotectant for Neonatal Brain Injury:
Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Christopher M. Traudt and Sandra E. Juul
8 Evaluating Effects of EPO in Rodent Behavioral Assays Related
to Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Catharine H. Duman and Samuel S. Newton
9 Erythropoietin and Cytoprotective Cytokines in Experimental Traumatic
Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Samson Kumar Gaddam, Jovany Cruz, and Claudia Robertson
10 Therapeutic Efficacy of Erythropoietin in Experimental Autoimmune
Encephalomyelitis in Mice, a Model of Multiple Sclerosis . . . . . . . . . . . . . . . 163
Ilaria Cervellini, Pietro Ghezzi, and Manuela Mengozzi
11 Deciphering the Intracellular Signaling of Erythropoietin
in Neuronal Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Murat Digicaylioglu
12 Assessment of Allodynia Relief by Tissue-Protective Molecules in a Rat Model
of Nerve Injury-Induced Neuropathic Pain. . . . . . . . . . . . . . . . . . . . . . . . . . 187
Maarten Swartjes, Marieke Niesters, and Albert Dahan
13 Intra-epidermal Nerve Fibers Density and Nociception in EPO-Treated
Type 1 Diabetic Rats with Peripheral Neuropathy. . . . . . . . . . . . . . . . . . . . . 197
Bianchi Roberto, Lombardi Raffaella, Porretta-Serapiglia Carla,
and Lauria Giuseppe
vii
viii Contents
14 ARA290 in a Rat Model of Inflammatory Pain . . . . . . . . . . . . . . . . . . . . . . . 213
Andrew Dilley
15 In Vivo Angiogenic Activity of Erythropoietin. . . . . . . . . . . . . . . . . . . . . . . . 227
Domenico Ribatti
16 Photoreceptor Degeneration in Mice: Adeno-Associated Viral
Vector-Mediated Delivery of Erythropoietin . . . . . . . . . . . . . . . . . . . . . . . . . 237
Pasqualina Colella and Alberto Auricchio
17 Myocardial Infarction: Cardioprotection by Erythropoietin. . . . . . . . . . . . . . 265
Mark I. Talan and Roberto Latini
18 Using Plethysmography to Determine Erythropoietin’s Impact on Neural
Control of Ventilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Tommy Seaborn, Max Gassmann, and Jorge Soliz
19 Cerebral Malaria: Protection by Erythropoietin. . . . . . . . . . . . . . . . . . . . . . . 315
Anne-Lise Bienvenu and Stephane Picot
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Contributors
ALBERTO AURICCHIO (cid:129) Telethon Institute of Genetics and Medicine (TIGEM),
Naples , Italy; Medical Genetics, Department of Medical Translational Science,
Federico II University, Naples , Italy
MYRIAM BERNAUDIN (cid:129) CERVOxy team “Hypoxia, cerebrovascular and tumoral
pathophysiologies”, UMR 6301-ISTCT, CNRS, CEA, Université de Caen
Basse-Normandie, CYCERON, Caen , France
ANNE-LISE BIENVENU (cid:129) Malaria Research Unit, SMITH ICBMS UMR CNRS,
UCBL, INSA Lyon, Lyon , France
ANNA YU. BOGDANOVA (cid:129) Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich
Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich ,
Switzerland
MICHAEL BRINES (cid:129) Araim Pharmaceuticals, Inc., Ossining, NY , USA
PORRETTA-SERAPIGLIA CARLA (cid:129) Neuromuscular Diseases Unit, IRCCS Foundation,
“Carlo Besta” Neurological Institute, Milan, Italy
ANTHONY CERAMI (cid:129) Araim Pharmaceuticals, Ossining, NY , USA;
Leiden University Medical Center, Leiden, The Netherlands
ILARIA CERVELLINI (cid:129) Brighton & Sussex Medical School, Falmer , UK
PASQUALINA COLELLA (cid:129) Telethon Institute of Genetics and Medicine (TIGEM),
Naples , Italy
DARRELL CONKLIN (cid:129) Department of Computer Science and Artifi cial Intelligence,
University of the Basque Country UPV/EHU, San Sebastián , Spain;
IKERBASQUE, Basque Foundation for Science, Bilbao , Spain
JOVANY CRUZ (cid:129) Baylor College of Medicine, Houston, TX , USA
ALBERT DAHAN (cid:129) Department of Anesthesiology , Leiden University Medical Center,
Leiden, The Netherlands
MURAT DIGICAYLIOGLU (cid:129) Departments of Neurosurgery and Physiology, University
of Texas Health Science Center, San Antonio, TX , USA
ANDREW DILLEY (cid:129) Brighton and Sussex Medical School, Falmer , UK
CATHARINE H. DUMAN (cid:129) Department of Psychiatry , Yale University School
of Medicine, New Haven, CT , USA
SERHAT ERBAYRAKTAR (cid:129) Department of Neurosurgery , School of Medicine, Dokuz Eylul
University, İnciralti, İzmir , Turkey
ZÜBEYDE ERBAYRAKTAR (cid:129) Department of Medical Biochemistry , School of Medicine,
Dokuz Eylul University, İnciralti, İzmir , Turkey
SAMSON KUMAR GADDAM (cid:129) Baylor College of Medicine, Houston, TX , USA
EITHAN GALUN (cid:129) Goldyne Savad Inst. of Gene Therapy, Hadassah Hebrew University
Hospital , Jerusalem, Israel
MAX GASSMANN (cid:129) Institute of Veterinary Physiology , Vetsuisse Faculty and Zurich
Center for Integrative Human Physiology (ZIHP), University of Zurich,
Zurich , Switzerland
ix
