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407 Pages·2016·13.27 MB·English
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Springer Series in Translational Stroke Research Jun Chen John H. Zhang Xiaoming Hu Editors Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke Springer Series in Translational Stroke Research Series Editor John Zhang More information about this series at h ttp://www.springer.com/series/10064 Jun Chen • John H. Zhang • Xiaoming Hu Editors Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke Editors Jun Chen John H. Zhang Department of Neurology Department of Anesthesiology University of Pittsburgh Loma Linda University School of Medicine Pittsburgh, PA , USA Loma Linda , CA , USA Pittsburgh Institute of Brain Disorders Department of Pharmacology and Recovery Loma Linda University School of Medicine University of Pittsburgh Loma Linda , CA , USA Pittsburgh , PA , USA Department of Physiology State Key laboratory of Medical Loma Linda University School of Medicine Neurobiology Loma Linda , CA , USA Fudan University Center for Neuroscience Research Shanghai , China Loma Linda University School of Medicine Loma Linda , CA , USA Xiaoming Hu Department of Neurology University of Pittsburgh Pittsburgh , PA, USA Pittsburgh Institute of Brain Disorders and Recovery University of Pittsburgh Pittsburgh , PA , USA State Key laboratory of Medical Neurobiology Fudan University Shanghai , China ISSN 2363-958X ISSN 2363-9598 (electronic) Springer Series in Translational Stroke Research ISBN 978-3-319-32335-0 ISBN 978-3-319-32337-4 (eBook) DOI 10.1007/978-3-319-32337-4 Library of Congress Control Number: 2016944470 © Springer International Publishing Switzerland 2016 T his 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. T he 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. T he 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 Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland Introduction: Nonneuronal Mech anisms and Targets for Stroke For several decades now, clinically effective neuroprotection has been an elusive goal. Although much progress has been made in terms of dissecting molecular path- ways and cellular mechanisms, true translation has not succeeded for patients suf- fering from stroke, brain trauma, and neurodegeneration. Excitotoxicity, oxidative stress, and programmed cell death all represent logical targets for preventing neuro- nal demise. But it is now increasingly apparent that saving neurons alone may not be enough. B ased on these challenges, the neurovascular unit was proposed as a conceptual framework for reassessing neuroprotection, the fundamental premise being that central nervous system (CNS) function is not solely based on neuronal activity. The brain is more than just action potentials! For neurotransmission to work, release– reuptake kinetics must be coordinated between neurons and astrocytes. For myelin- ated signals to connect different brain networks, axons need to be in constant homeostatic communication with oligodendrocytes. For the blood–brain barrier to be manifested, crosstalk is required between glial endfeet and cerebral endothelium. Altogether, CNS function is based on cell–cell signaling between multiple cells. Therefore, neuroprotection requires one to do much more than just prevent neuronal death. Rescuing function and cell–cell crosstalk between all cell types in neuronal, glial, and vascular compartments should be required. It is in this context that this monograph N onneuronal Mechanisms of Brain Damage and Repair After Stroke represents a signifi cant addition to the literature and fi eld. This monograph is divided into fi ve well-integrated sections. The fi rst section focuses on microvascular integrity. Chapters here include analyses of the structural biology of tight junctions, the role of pericytes, glial regulation of barrier function, blood–brain barrier damage in neonatal stroke, and a reconsideration of angiogen- esis after stroke. The second section covers the complex actions of glial cells and includes chapters on astrocyte protection, biphasic effects of microglia, and cross- talk between cerebral endothelium and oligodendrocyte precursor cells. The third section then goes on to examine the multifactorial pathways in stroke neuroinfl am- mation, with analyses of peripheral immune activators, monocyte/macrophage responses, T cells, B cells, mast cells and neutrophils, and the web of cytokines that v vi Introduction: Nonneuronal Mechanisms and Targets for Stroke all contribute to stroke pathophysiology. A critical part of stroke that is relatively less investigated comprises white matter response, and this is the focus of the fourth section of the monograph. In this section, chapters are devoted to assessing the age dependence of white matter injury and subsequently investigating the role of oligo- dendrogenesis for white matter plasticity. Finally, the last collection of chapters builds on the mechanistic themes explored thus far to develop potential therapeutic approaches. In this fi nal section, chapters span a comprehensive range, including the targeting of leukocyte–endothelial interactions, methods to repair the entire neu- rovascular unit, immune-based treatments, and cell-based therapies that all seek to achieve neuroprotection by restoring crosstalk amongst the nonneuronal population of CNS cells. T aken together, the chapters here represent the very best in cutting-edge hypoth- eses and translational ideas. The mechanisms dissected herein may eventually lead us to testable targets for stroke patients. Curated by editors and authors who are experts in their fi eld, this is an impressive collection of stroke science. Eng H. Lo, Ph.D. [email protected] Neuroprotection Research Laboratory Department of Radiology Massachusetts General Hospital and Harvard Medical School 149 13th Street , Charlestown , MA , 02129 , USA Contents Part I Microvascular Integrity in Stroke Structural Alterations to the Endothelial Tight Junction Complex During Stroke .................................................................................. 3 Anuska V. Andjelkovic and Richard F. Keep Role of Pericytes in Neurovascular Unit and Stroke ................................... 25 Turgay Dalkara , Luis Alarcon-Martinez , and Muge Yemisci Glial Support of Blood–Brain Barrier Integrity: Molecular Targets for Novel Therapeutic Strategies in Stroke................................................... 45 Patrick T. Ronaldson and Thomas P. Davis Barrier Mechanisms in Neonatal Stroke ...................................................... 81 Zinaida S. Vexler Angiogenesis: A Realistic Therapy for Ischemic Stroke ............................. 93 Ke-Jie Yin and Xinxin Yang Part II Glial Cells in Stroke Astrocytes as a Target for Ischemic Stroke ................................................... 111 Shinghua Ding Microglia: A Double-Sided Sword in Stroke ................................................ 133 Hong Shi , Mingyue Xu , Yejie Shi , Yanqin Gao , Jun Chen , and Xiaoming Hu Crosstalk Between Cerebral Endothelium and Oligodendrocyte After Stroke ..................................................................................................... 151 Akihiro Shindo , Takakuni Maki , Kanako Itoh , Nobukazu Miyamoto , Naohiro Egawa , Anna C. Liang , Takayuki Noro , Josephine Lok , Eng H. Lo , and Ken Arai vii viii Contents Part III Peripheral Immune Cells in Stroke The Peripheral Immune Response to Stroke ................................................ 173 Josef Anrather The Role of Spleen-Derived Immune Cells in Ischemic Brain Injury ....... 189 Heng Zhao Regulatory T Cells in Ischemic Brain Injury ............................................... 201 Arthur Liesz B-Cells in Stroke and Preconditioning- Induced Protection Against Stroke ................................................................................................. 217 Uma Maheswari Selvaraj , Katie Poinsatte , and Ann M. Stowe Mast Cell as an Early Responder in Ischemic Brain Injury ....................... 255 Perttu J. Lindsberg , Olli S. Mattila , and Daniel Strbian Roles of Neutrophils in Stroke ....................................................................... 273 Glen C. Jickling and Frank R. Sharp The Function of Cytokines in Ischemic Stroke ............................................ 303 Christopher C. Leonardo and Keith R. Pennypacker Part IV White Matter Injury and Repair in Stroke Ischemic Injury to White Matter: An Age- Dependent Process .................. 327 Sylvain Brunet , Chinthasagar Bastian , and Selva Baltan Part V Emerging Therapies to Target Non- neuronal Mechanisms After Stroke Neurovascular Repair After Stroke .............................................................. 347 Sherrefa R. Burchell , Wing-Mann Ho , Jiping Tang , and John H. Zhang The Role of Nonneuronal Nrf2 Pathway in Ischemic Stroke: Damage Control and Potential Tissue Repair .............................................. 377 Tuo Yang , Yang Sun , and Feng Zhang Stem Cell Therapy for Ischemic Stroke ........................................................ 399 Hung Nguyen , Naoki Tajiri , and Cesar V. Borlongan Contributors Luis Alarcon-Martinez , B.Sc., M.Sc., Ph.D. Institute of Neurological Sciences and Psychiatry , Hacettepe University , Ankara , Turkey Anuska V. Andjelkovic , M.D., Ph.D. Department of Pathology , University of Michigan , Ann Arbor , MI , USA D epartment of Neurosurgery, U niversity of Michigan Health System, A nn Arbor, MI , USA Josef Anrather Feil Family Brain and Mind Research Institute, Weill Cornell Medical College , New York , NY , USA Ken Arai Neuroprotection Research Laboratory, Departments of Radiology and Neurology, M assachusetts General Hospital and Harvard Medical School, Charlestown , MA , USA Selva Baltan , M.D., Ph.D. Department of Molecular Medicine , Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland , OH , USA D epartment of Neurosciences, L erner Research Institute, Cleveland Clinic Foundation , Cleveland , OH , USA Chinthasagar Bastian , M.B.B.S., Ph.D. Department of Neurosciences , Lerner Research Institute, Cleveland Clinic Foundation , Cleveland , OH , USA Cesar V. Borlongan D epartment of Neurosurgery and Brain Repair, U niversity of South Florida Morsani College of Medicine , Tampa , FL , USA Sylvain Brunet , B.Sc., Ph.D. Department of Molecular Medicine , Cleveland Clinic Lerner College of Medicine of Case Western Reserve University,, C leveland, OH , USA D epartment of Neurosciences, L erner Research Institute, Cleveland Clinic Foundation , Cleveland , OH , USA ix

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This book provides a comprehensive overview of the latest research in the role of non-neuronal cells - astrocytes, oligodendrocytes, endothelial cells, pericytes, microglia, and other immune cells in ischemic brain injury and long-term recovery. In these cases, neurodegeneration and brain repair are
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