Biomarkers of Brain Injury and Neurological Disorders TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk Biomarkers of Brain Injury and Neurological Disorders Editors Kevin K.W. Wang Zhiqun Zhang Firas H. Kobeissy Center for Neuroproteomics and Biomarkers Research Department of Psychiatry The Evelyn F. and William L. McKnight Brain Institute University of Florida Gainesville, FL USA p, A SCIENCE PUBLISHERS BOOK GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM Front Cover Art Work: The Art work is designed by the Graphic designer Hussein Mokdad, B.S. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Dedication To my family, for the love and patience they provide me. Kevin K.W. Wang For my husband Jianghui Chao, our wonderful children Ryan and Arnall, my parents, sisters and loved ones who supported and believed in me. Zhiqun Zhang To my mom Kawsar; may her soul rest in peace, my dear dad Hosni, and Sister Maha whose love and patience gave me hope in my path. To my mentors, Dr. Kevin K. Wang & Dr. Mark S. Gold whose experience and advice drove my success…. Firas H. Kobeissy TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk Foreword The central nervous system, including the brain and spinal cord, is arguably the most complex human organ system in terms of structure and function. This book stands out in describing the latest biomarker studies in brain disorders relevant to its mechanism, advanced technologies, experimental methods, and clinical trial studies. Diagnostic tests based on biomarkers have already demonstrated proven clinical diagnostic utility in acute care environments. For example, in the area of cardiac injury, cardiac troponin proteins (T and I) and various forms of brain natriuretic peptide (BNP), often in combination with other biomarkers, are routinely used to facilitate accurate diagnosis of congestive heart failure and myocardial infarction, in patients presenting with chest pain. Recently, there has been broad recognition that biomarkers can also play a critical role in drug discovery and development. There are several areas in which biomarkers can facilitate brain injury drug development and eventually personalized medicine. Biomarker research methods may improve our knowledge of the pathobiology that ensues after CNS disorders, and unlock the connections between this pathology, individual variability, and the heterogeneous outcomes experienced by those with central nervous system disorders. The aim of this book is to draw together the work of leading experts in the fi elds of neurological disorders, brain injury, and drug abuse and to highlight what is known on a broad range of topics pertaining to biomarkers in central nervous system disorders ranging from traumatic brain injury, spinal cord injury, multiple sclerosis, and alcohol abuse. This elegant volume begins with chapters discussing basic mechanisms and methods of biomarker identifi cation including neuroproteomics analysis, followed by surveying different textures of currently novel biomarkers such as microRNA, proteins as well as genetic fi ngerprints and their applications in different neurological disorders. This section is then followed by elaborate chapters written by w orld-renowned experts, who have tackled several neurodegenerative diseases specifi cally, along with their mechanisms and their associated “known” biomarkers. This work fl ows smoothly, discussing novel methods such as Deep Brain Stimulation, the endpoint of which can viii Biomarkers of Brain Injury and Neurological Disorders be used as a neurotherapeutic marker for a number of neuropsychiatric disorders. The book concludes by emphasizing the implications and importance of biomarker research on several fi elds, such as brain trauma, drug addiction and the need for theranostic (therapeutic and diagnostic) biomarker approaches. It is my great honor that three of our faculty at the Department of Psychiatry (Wang, Zhang and Kobeissy), who are experts in the areas of biomarkers in brain injury studies and drug abuse–associated neurotoxicity, have gathered in this respected work to deliver one of the most updated presentations in biomarker studies. This collection will have direct implications on neurotherapeutic management, treatment guidance, as well as indicators of injury severity and prognosis. The book will lay out a foundation for scholars interested in several neurological disorders and related biomarker research. This is currently a unique and timely volume that will provide a comprehensive review for basic scientists, graduate students, medical students, clinical researchers and medical professionals with interest in translational research in the area of brain injury and other brain disorders. Mark S. Gold, MD University of Florida Alumni Distinguished Professor (2011–2015) University of Florida Distinguished Professor Donald R. Dizney Eminent Scholar University of Florida College of Medicine and McKnight Brain Institute Departments of Psychiatry, Neuroscience, Anesthesiology Community Health & Family Medicine Chairman, Department of Psychiatry Preface Studies in the fi eld of central nervous system (CNS) biomarkers have been evolving at quite a rapid pace especially with the introduction of novel high throughput screening techniques such as proteomics and microarrays coupled with systems biology with its predictive potential of missed targets and their dynamic alteration in respect to disease progression. This in turn has led to the identifi cation of a new generation of biomarkers including signature microRNA biomarkers and even autoantibodies serving as indirect specifi c indicators of certain brain injury disorders. This exciting advance in biomarker research has encouraged new lines of funding from national and private sectors aiming at identifying novel treatment targets driven via biomarker identifi cation. Among the most challenging and highly demanding fi elds for biomarker research is the CNS and particularly those related to brain trauma pathology. The CNS, including the brain and spinal cord, is arguably the most complex human organ system in terms of structure and function. Of interest, biomarker identifi cation of CNS disorders is considered the Holy Grail that is in constant pursuit by scientists and medical doctors. Identifying these markers in body fl uids represents a major challenge due to several factors including their minute levels, turn over/clearance rate, dynamic range in serum/cerebrospinal fl uid, etc. which necessitates the use of high throughput technologies such as genomics, neuroproteomics and recently microRNA assessment to decipher these markers dynamics. In the area of confl icts worldwide, brain injury has been designated the “signature injury” of current military confl icts. CNS trauma primarily from regular accidents or sport associated injury as well as battlefi eld represents one of the most common causes of morbidity and mortality in our society with enormous societal and economic burdens. Each year, approximately three million people sustain traumatic brain injury; these are often present with neuropsychological defi cits that may develop later at chronic phases; coupled with altered emotional, and/or cognitive impairments, exhibiting decreased executive function, depression, and signifi cant drug