Oxford Neurovascular Medicine Pursuing Cellular Longevity For Healthy Aging

NEUROVASCULAR MEDICINE This page intentionally left blank Neurovascular Medicine Pursuing Cellular Longevity for Healthy Aging Kenneth Maiese, MD Division of Cellular and Molecular Cerebral Ischemia Departments of Neurology and Anatomy & Cell Biology Barbara Ann Karmanos Cancer Institute Center for Molecular Medicine and Genetics Institute of Environmental Health Sciences Wayne State University School of Medicine Detroit, MI 1 2009 3 Oxford University Press, Inc., publishes works that further Oxford University’s objective of excellence in research, scholarship, and education. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Copyright © 2009 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York 10016 www.oup.com Oxford is a registered trademark of Oxford University Press All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Oxford University Press. Library of Congress Cataloging-in-Publication Data Neurovascular medicine: pursuing cellular longevity for healthy aging / [edited by] Kenneth Maiese. p. ; cm. Includes bibliographical references and index. ISBN 978-0-19-532669-7 1. Pathology, Cellular. 2. Pathology, Molecular. 3. Nervous system—Degeneration. 4. Inflammation—Mediators. I. Maiese, Kenneth, 1958- [DNLM: 1. Nervous System Physiology. 2. Aging—physiology. 3. Cell Physiology. 4. Neurodegenerative Diseases—prevention & control. 5. Neurons—physiology. WL 102 N5122 2008] RB113.N48 2008 616.07—dc22 2008006253 9 8 7 6 5 4 3 2 1 Printed in China on acid-free paper Preface It is estimated that more than 500 million individuals suffer from nervous and vascular system disorders in the world. These disorders can comprise both acute and chronic degenerative diseases that involve hypertension, cardiac insufficiency, stroke, traumatic brain injury, presenile dementia, Alzheimer’s disease, and Parkinson’s disease. In regards to metabolic disorders such as diabetes mellitus, diabetes itself is present in more than 165 million individuals worldwide, and by the year 2030, it is predicted that more than 360 million individuals will be affected by diabetes mellitus. Of potentially greater concern is the incidence of undiagnosed diabetes that consists of impaired glucose tolerance and fluctuations in serum glucose levels that can increase the risk for acute and long-term complications in the vascular and cardiac systems. Considering the significant risks that can be presented to the nervous and vascular systems, it is surprising to learn that organs such as the brain are highly susceptible to loss of cellular function and have only limited capacity to avert cellular injury. A variety of observations support this premise. For example, the brain possesses the highest oxygen metabolic rate of any organ in the body, consuming 20% of the total amount of oxygen in the body and enhancing the possibility for the aberrant generation of free radicals. In addition, the brain is composed of significant amounts of unsaturated fats that can readily serve as a source of oxygen free radicals to result in oxidative stress. Although a number of mechanisms can account for the loss of neuronal and vascular cells, the generation of cellular oxidative stress represents a significant component for the onset of pathological complications. Initial work in this field by early pioneers obser