Cerebral Blood Flow, Metabolism, and Head Trauma
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1 Cerebral Blood Flow, Metabolism, and Head Trauma
2
3 Christian W. Kreipke Editors Jose A. Rafols Cerebral Blood Flow, Metabolism, and Head Trauma The Pathotrajectory of Traumatic Brain Injury
4 Editors Christian W. Kreipke John D. Dingell VA Medical Center Research and Development Service Detroit, MI, USA Jose A. Rafols Department of Anatomy and Cell Biology Wayne State University School of Medicine Detroit, MI, USA ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi 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. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
5 Preface Traumatic brain injury (TBI) has caught the ear of the general public in the last few years in the context of injuries seen both in the athletes and the military. Household names such as Crosby and Ali resound of the association with TBI. Yet, the mere heightened awareness of TBI of late does not obviate the fact that it has been situated as a critical problem in society, especially in children and the elderly, for multiple decades. Despite this, the underlying pathotrajectory of TBI has only recently been truly appreciated. Furthermore, over 25 attempts at determining a treatment for TBI have resulted in a disappointing failure to achieve any signi fi cant relief for head trauma patients. Much of this failure to develop cures may be, in part, due to the only recent development of better models of TBI that more closely recapitulate the human condition, the recent advances in our ability to image pathophysiological sequelae in the brain following TBI, a more recent emphasis on studying the vascular dysfunction that accompanies head trauma, and a very recent understanding of how age and sex can alter outcome to brain injury. While this book was developed to satisfy a wide audience, from patient to caregiver, basic scientist to clinical scientist, the overall goal is to present the most current information known about head trauma and to expose areas where we may be de fi cient in understanding the nuances of TBI. In particular, focus will be placed on the largest gap in our knowledge the in fl uence of cerebral blood fl ow (CBF) and metabolism in outcome following injury. Thus, Chap. 1 will present a brief history of our understanding of brain injury and will present blood fl ow in the context of its more recent history in TBI investigations. Chapter 2 will focus primarily on what is currently known about the in fl uence of CBF in the pathotrajectory of TBI. Chapter 3 will present a brief overview of modeling TBI as a means to understand the underlying pathological state associated with brain injury victims, while Chap. 4 will introduce new concepts of disrupted vasculature following head trauma that can only be appreciated through more advanced imaging techniques that have been developed in the past few years. Chapter 5 will become more focused on the vasoreactive substances underlying disrupted blood fl ow. Chapter 6 will provide both basic science and clinical evidence that age and sex in fl uence outcome after injury. Finally, Chap. 7 will provide the latest preclinical rationale for focusing on CBF and v
6 vi Preface strategies to improve blood fl ow as a means to improve outcome in patients suffering the effects of TBI. Taken together, the information contained in the following work is designed to both educate and illuminate anyone associated with TBI, with the hope that the information contained within will stimulate future work that may, in the near future, lead to effective therapies to mitigate the societal burdens, both fi nancial and emotional, and negative outcome of TBI. Detroit, MI, USA Christian Kreipke, PhD
7 Contents 1 Historical Perspectives in Understanding Traumatic Brain Injury and in Situating Disruption in CBF in the Pathotrajectory of Head Trauma... 1 Christopher Betrus and Christian W. Kreipke 2 Situating Cerebral Blood Flow in the Pathotrajectory of Head Trauma Justin Graves, Christopher Betrus, and Jose A. Rafols 3 Modeling of Traumatic Brain Injury and its Implications in Studying the Pathology of Repeated Mild Impacts to the Head Michael J. Kane, Mariana Angoa Pérez, Denise I. Briggs, David C. Viano, Christian W. Kreipke, and Donald M. Kuhn 4 The Presence of Venous Damage and Microbleeds in Traumatic Brain Injury and the Potential Future Role of Angiographic and Perfusion Magnetic Resonance Imaging E.M. Haacke, Waqar Raza, Bo Wu, and Zhifeng Kou 5 Situating the Endothelin System in the Pathotrajectory of TBI-Induced Changes in Hemodynamics Anthony Kropinski, Paula Dore-Duffy, and Christian W. Kreipke 6 Age and Sex Differences in Cerebral Blood Flow and Autoregulation after Pediatric Traumatic Brain Injury William M. Armstead and Monica S. Vavilala vii
8 viii Contents 7 New Frontiers in Clinical Trials Aimed at Improving Outcome Following Traumatic Brain Injury Christian W. Kreipke, Anthony Kropinski, Justin Graves, David Tiesma, Michael Kaufman, Steven Schafer, William M. Armstead, Paula Dore-Duffy, and Donald M. Kuhn Index
9 Contributors William M. Armstead, PhD Departments of Anesthesiology and Critical Care and Pharmacology, University of Pennsylvania, Philadelphia, PA, USA Christopher Betrus, BS Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Denise I. Briggs, BS Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, John D. Dingell VA Medical Center, Research and Development Service, Detroit, Paula Dore-Duffy, PhD Department of Neurology, Wayne State University School of Medicine, Detroit, Justin Graves, BA Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, E.M. Haacke, PhD Department of Radiology, Wayne State University, Detroit, Michael J. Kane, PhD Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, John D. Dingell VA Medical Center, Research and Development Service, Detroit, Michael Kaufman, BS Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Zhifeng Kou, PhD Department of Radiology, Wayne State University, Detroit, ix
10 x Contributors Christian W. Kreipke, PhD John D. Dingell VA Medical Center, Research and Development Service, Detroit, Anthony Kropinski, BS Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Donald M. Kuhn, PhD Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, John D. Dingell VA Medical Center, Research and Development Service, Detroit, Mariana Angoa Pérez, PhD Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, John D. Dingell VA Medical Center, Research and Development Service, Detroit, Jose A. Rafols, PhD Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Waqar Raza, MS Department of Radiology, Wayne State University, Detroit, Steven Schafer, BS Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, David Tiesma, BS Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Monica S. Vavilala, MD Department of Anesthesiology, Harborview Medical Center, University of Washington, Seattle, WA, USA Department of Pediatrics, Harborview Medical Center, University of Washington, Seattle, WA, USA David C. Viano, PhD ProBiomechanics LLC, Bloomfield Hills, Department of Biomedical Engineering, School of Engineering, Wayne State University, Detroit, Bo Wu, BS Department of Radiology, Wayne State University, Detroit,
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