Table Of ContentSpringer Series in Translational Stroke Research
Paul A. Lapchak
John H. Zhang Editors
Neuroprotective
Therapy for
Stroke and
Ischemic Disease
Springer Series in Translational Stroke Research
Series Editor
John Zhang
Loma Linda, USA
More information about this series at http://www.springer.com/series/10064
Paul A. Lapchak • John H. Zhang
Editors
Neuroprotective Therapy
for Stroke and Ischemic
Disease
Editors
Paul A. Lapchak John H. Zhang
Department of Neurology and Neurosurgery Loma Linda University School of Medicine
Cedars-Sinai Medical Center Loma Linda, CA, USA
Los Angeles, CA, USA
ISSN 2363-958X ISSN 2363-9598 (electronic)
Springer Series in Translational Stroke Research
ISBN 978-3-319-45344-6 ISBN 978-3-319-45345-3 (eBook)
DOI 10.1007/978-3-319-45345-3
Library of Congress Control Number: 2016955837
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Preface
This is a very timely compilation of cutting-edge aspects of neuroprotective therapy
for ischaemic stroke in a myriad of clinical and experimental situations. It was
assembled by basic and clinical scientists at a time well after the dust had settled on
the subject, following the difficulties of translating neuroprotection from bench to
bedside. However, we are still mystified as to why this translational gap persists
although numerous possible explanations have been given, in what now must be
thousands of review articles. The book is logically and easily divided into four sec-
tions, ranging from the historical aspects of neuroprotection right through to the
very latest aspects of clinical trial design.
Several positives have come from the difficulties experienced in translation of
neuroprotective therapies, and these are all brought out nicely in this volume. First,
there is now a vastly increased rigour in preclinical trial design which led to the
STAIR (Stroke Treatment Academic Industry Roundtable) series of recommenda-
tions. These have provided valuable benchmarks for all those now conducting
research in this area. Second, the idea of aggregating preclinical animal model data
using meta-analysis techniques as used in the clinical sphere was pioneered by the
Melbourne and Edinburgh groups led by Malcolm McLeod and David Howells,
which later exposed problems with sample sizes, publication bias and lack of blind-
ing as only some of the issues that need to be addressed to improve the quality of the
preclinical research data. These findings have increased the likelihood of translation
into the clinic. The Melbourne and Edinburgh groups have formalised their efforts
in this area with the CAMARADES (Collaborative Approach to Meta-Analysis and
Review of Animal Data from Experimental Studies) collaboration which acts as a
preclinical form of the Cochrane Collaboration. The groups have also published
guidelines for experimental design in a number of journals; indeed the movement
has become so influential that other research disciplines are rapidly following suit.
Third, translational failures are stimulating the search for new therapeutic targets
such as autophagy as well as existing pathways and processes such as uric acid
metabolism and the immune system.
v
vi Preface
An important component of the book is the recognition that modern endovascu-
lar treatment and its ischaemic consequences play an important part in the
neuroprotection story. Indeed, the entirety of Sect. 4 is dedicated to combination
therapies. Clearly, the outstanding success of recanalisation approaches with devices
has re-energised the debate about reperfusion injury. There already existed an exten-
sive experimental background well before these interventions were shown to be so
clinically successful. On balance, the likelihood that an effective form of neuropro-
tection of clinical importance would arise from this type of research would seem to
be quite high. Time will tell.
The compilation of such a complete range of aspects of neuroprotection raises
the question as to whom the readership should be directed and who would most
benefit. It certainly would be an ideal reference for any current researcher in any
aspect of neuroprotection, either experienced or just beginning. It would also be a
useful compendium for interested students, clinicians or scientists from other disci-
plines who’d like to dip into its rich matrix.
The quality of the information assembled shines through the experiences of the
authors who are clearly leaders in their field. This alone makes this volume one that
anyone would be proud to have on their bookshelf or, as is often the case today,
readily accessible on their laptop.
Melbourne, VIC, Australia Geoffrey A. Donnan
2016
Contents
Part I Stroke Neuroprotection: The History
and Learning Experience
1 Reflections on Neuroprotection Research and the Path
Toward Clinical Success ......................................................................... 3
Paul A. Lapchak and Paul D. Boitano
2 Systematic Review and Meta-analysis: Important Tools
in Understanding Drug Development for Stroke ................................. 73
Sarah K. McCann, Emily S. Sena, Gillian L. Currie,
Malcolm R. Macleod, and David W. Howells
3 Neuroprotection Is Technology, Not Science ........................................ 95
Donald J. DeGracia, Doaa Taha, Fika Tri Anggraini,
and Zhi-Feng Huang
4 History of Experimental Stroke Research ............................................ 123
Victoria E. O’Collins
5 History of Neuroprotection: Trials and Tribulations ........................... 133
Ali Razmara and Steven C. Cramer
Part II Novel Neuroprotection Mechanisms and Targets
6 Targeting PSD-95 as a Novel Approach in the Treatment
of Stroke ................................................................................................... 157
Linda M. Haugaard-Kedström, Eduardo F.A. Fernandes,
and Kristian Strømgaard
7 ATP-Sensitive Potassium Channels (K ) Play a Role
ATP
in Hypoxic Preconditioning Against Neonatal Hypoxic-Ischemic
Brain Injury ............................................................................................. 185
Zhong-Ping Feng and Hong-Shuo Sun
vii
viii Contents
8 Targeting Oxidative Stress in Stroke ..................................................... 203
Anders Bach
9 Nitrones, Old Fellows for New Therapies in Ischemic Stroke ............ 251
Alejandro Escobar-Peso, Mourad Chioua, Valerio Frezza,
Emma Martínez-Alonso, José Marco-Contelles, and Alberto Alcázar
10 Neuroprotective Strategies via Modulation of Innate
Immune Receptors .................................................................................. 285
George Trendelenburg
11 Harnessing the Power of the Human Immune System via Multi-omic
Immune Profiling in Stroke Treatment and Recovery ........................ 293
Taura L. Barr, V. Gionis, and R. Giersch
12 Polarization of Microglia/Macrophages in Brain Ischaemia:
Relevance for Stroke Therapy ............................................................... 303
Diana Amantea, Rosaria Greco, Cristina Tassorelli,
and Giacinto Bagetta
13 Endoplasmic Reticulum Stress: An Opportunity
for Neuroprotective Strategies After Stroke ......................................... 329
Morgane Louessard, Eloise Lemarchand, Carine Ali, Denis Vivien,
and Benoit Denis Roussel
14 Effects of Neuroprotectants Before and after Stroke:
Statins and Anti-Hypertensives ............................................................. 349
Roberto Federico Villa, Federica Ferrari, and Antonio Moretti
15 Toward Effective Combination Therapy and Pleiotropic Drugs ........ 401
Sergio Amaro, Xabier Urra, and Ángel Chamorro
16 TRPM7 Channels as Potential Therapeutic Targets for Stroke ......... 415
Hong-Shuo Sun and Zhong-Ping Feng
17 Cholinergic Protection in Ischemic Brain Injury ................................. 433
Victor V. Uteshev
18 Remote Ischemic Conditioning: A Highly Translatable
Therapy for Acute Stroke ....................................................................... 459
Chizoba J. Ezepue and David C. Hess
19 Hypothermia for Acute Ischemic Stroke .............................................. 477
Roy Poblete and Gene Sung
20 Modern Endovascular Treatment of Ischemic Disease ....................... 501
Steven L. Gogela, Todd A. Abruzzo, and Mario Zuccarello
21 Cerebral Microbleeds and Thrombolysis
for Acute Ischemic Stroke ...................................................................... 527
JungSeok Lee and Mark Fisher
Contents ix
22 Targeting Pericytes and the Microcirculation
for Ischemic Stroke Therapy.................................................................. 537
Ain A. Neuhaus, Brad A. Sutherland, and Alastair M. Buchan
Part III Thrombolysis and Embolectomy
23 Thrombolytic and Endovascular Therapies
for Acute Ischemic Stroke ...................................................................... 559
Hormozd Bozorgchami and Helmi L. Lutsep
24 Sonothrombolysis for Acute Ischemic Stroke:
A Critical Appraisal ................................................................................ 593
Georgios Tsivgoulis, Apostolos Safouris, and Andrei V. Alexandrov
25 Combination Therapy with Thrombolysis ........................................... 607
Burak Yulug and Wolf-Rüdiger Schäbitz
26 Oxygen Carriers: Are they Enough for Cellular Support? ................ 621
Jennifer L.H. Johnson
27 A New Paradigm in Protecting Ischemic Brain: Preserving
the Neurovascular Unit Before Reperfusion ......................................... 641
Natacha Le Moan, Philberta Y. Leung, Natalia Rost,
Jonathan A. Winger, Ana Krtolica, and Stephen P. Cary
Part IV Stroke Models and Clinical Trial Considerations
28 The Right Rodent for the Job: Infarct Variability
Between Strains and Its Impact on Logistics
of Experimental Animal Studies ............................................................ 667
Sarah Rewell and David W. Howells
29 Rabbit Spinal Cord Ischemia Model for the Development
of Neuroprotective Treatments .............................................................. 689
Daisy Chou, Anja Muehle, Paul A. Lapchak, and Ali Khoynezhad
30 Stroke Sex Differences: From Basic Research
to Clinical Trials ...................................................................................... 701
Claire L. Gibson, Philip M.W. Bath, and Raeed Altaee
31 Unpuzzling the Comorbid Type 2 Diabetes
and Hypertension-Related Cognitive Dysfunction and Stroke ........... 711
I. Sebastião, E. Candeias, M.S. Santos, C.R. Oliveira, Paula I. Moreira,
and Ana I. Duarte
32 Sex-Specific Factors in Stroke ................................................................ 733
Anjali Chauhan, Hope Moser, and Louise D. McCullough
x Contents
33 Current Imaging Strategies for Patient Selection
in Acute Ischemic Stroke Trials ............................................................. 751
Jenny P. Tsai and Gregory W. Albers
Index ................................................................................................................. 775
