BRAIN DAMAGE – BRIDGING BETWEEN BASIC RESEARCH AND CLINICS Edited by Alina González-Quevedo Brain Damage – Bridging Between Basic Research and Clinics Edited by Alina González-Quevedo Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Marina Jozipovic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Brain Damage – Bridging Between Basic Research and Clinics, Edited by Alina González-Quevedo p. cm. ISBN 978-953-51-0375-2 Contents Preface IX Chapter 1 The Etiology and Evolution of Fetal Brain Injury 1 Andrew Macnab Chapter 2 Brain Damage and Long-Lasting Sequels in Childhood: What Does Cerebral Palsy (CP) Mean at the Beginning of the XXI Century? 39 D. Truscelli Chapter 3 Inborn Errors of Metabolism and Brain Involvement – 5 Years Experience from a Tertiary Care Center in South India 57 Kannan Vaidyanathan, M. P. Narayanan and D. M. Vasudevan Chapter 4 Demonstration of Subclinical Organ Damage to the Central Nervous System in Essential Hypertension 79 Alina González-Quevedo, Sergio González García, Otman Fernández Concepción, Rosaralis Santiesteban Freixas, Luis Quevedo Sotolongo, Marisol Peña Sánchez, Rebeca Fernández Carriera and Zenaida Hernández Chapter 5 Pathology of Neurodegenerative Diseases 99 YoungSoo Kim, Yunkyung Kim, Onyou Hwang and Dong Jin Kim Chapter 6 Nitrooxidative Stress and Neurodegeneration 139 Michal Fiedorowicz and Pawel Grieb Chapter 7 Molecular Mechanisms of Acute Brain Injury and Ensuing Neurodegeneration 163 Francisco J. Ortega, Jose M. Vidal-Taboada, Nicole Mahy and Manuel J. Rodríguez Chapter 8 Transmissible Spongiform Encephalopathies 187 Glaucia N. M. Hajj, Tiago G. Santos, Michele C. Landemberger and Marilene H. Lopes VI Contents Chapter 9 Cognitive Impairments in Drug Addicts 221 Fred Nyberg Chapter 10 Brain Restoration: A Function of Sleep 245 Eva Acosta-Peña, Juan Carlos Rodríguez-Alba and Fabio García-García Chapter 11 Dynamic Brain Function Monitoring a New Concept in Neuro-Intensive Care 257 E. Bosco and P. Zanatta Chapter 12 Carotid Endarterectomy 273 Mustafa Karaçelik Preface Brain damage or brain injury are very ample terms which include the destruction or degeneration of brain cells as a consequence of a wide range of internal and external factors, resulting from acute events (stroke, epilepsy or head injury) or by chronic degeneration as in Alzheimer's and Parkinson's Disease. Nevertheless, although the primary insult leading to brain damage can be distinctly different, the mechanisms underlying the death of neurons and glial cells in the brain have many common interrelated pathways (hypoxia, oxidative damage, excitotoxicity, and inflammation, among others). It should also be taken into account that when brain tissue is damaged, cells often continue to die after the initial stimulus has stopped. Thus, understanding the pathophysiological mechanisms of brain damage in different pathological settings is crucial not only to mitigate the effect of the primary insult on the brain, but also to find a way of stopping this cascade of cell death. “Brain damage- bridging between basic research and clinics” is a book that provides an insight into this very broad area of research, focusing on topics that deal with some of the main problems confronted by modern neurosciences, spanning through neurodevelopmental and neurodegenerative disorders, changes observed in drug addictions and sleep deprivation, as well as early assessment of brain injury for preventive strategies employing sensitive biomarkers. The first chapter deals with the etiology and evolution of fetal brain damage, reviewing the main and varied causes leading to it: genetic anomalies, nutritional deficiencies, environmental factors (alcohol, addictive drugs, and nicotine among others), prematurity, maternal illness during pregnancy, fetal inflammatory response syndrome and hypoxia. Hypoxia is central to the genesis of a significant proportion of brain injury occurring in the fetus, which gives way to a spectrum of long term brain morbidity ranging from mild motor and cognitive defects to cerebral palsy and severe cognitive disabilities. Prevention and management of fetal brain injury are topics also considered in some detail. Cerebral palsy (CP), one of the most devastating consequences of fetal or perinatal brain injury - with a high cost to the child, the family and society -is considered in Chapter 2. Despite the technological advances that have decreased mortality in term and preterm infants, the worldwide prevalence of CP is 1.5 to 2.0 cases per 1000 births, a rate that has remained constant for nearly 40 years. X Preface Chapter 3 deals with the toll of inborn errors of metabolism on the brain, through the experience accumulated in South India. Many body systems are affected in these disorders, but the predominant damage will be to the central nervous system (CNS). Conducting metabolic screening to diagnose and treat them early in life is of utmost importance in order to avoid irreversible damage to the brain. As the average life span has been extended by the fast growing medical technologies, the elderly population is increasing rapidly, and with it the prevalence of age-related neurodegenerative diseases. In the following 5 chapters, mechanisms through which brain damage occurs in different neurological conditions are evaluated. First of all, the importance of detecting subclinical target organ damage to the brain in essential hypertension is highlighted in chapter 4, as it is known to be the most important risk factor for developing stroke and vascular dementia. Chapter 5 reviews the current understanding of the etiology and pathogenesis of Alzheimer´s Disease (AD) and Parkinson´s Disease (PD), with an emphasis on protein abnormalities and particular vulnerability of the nigral dopaminergic neurons, and the efforts that are being made for the development of disease-modifying therapies. In chapter 6 the way in which nitrooxidative stress can contribute to major neurodegenerative diseases – such as AD, PD and glaucoma – is considered, as well as the rationales and precautions that should be evaluated when designing antioxidant therapies. Another aspect of neurodegeneration is evaluated in chapter 7, where acute injury to the CNS – including stroke and traumatic brain and spinal cord injury – is shown to activate a neurodegenerative process whose effects are time-dependent and related to the initial severity of the primary insult. Accumulating evidence implicates protein misfolding and aggregation as a likely common underlying cause for protein conformational disorders which include AD, PD, Huntington’s disease, polyglutamine disorders, amyotrophic lateral sclerosis, and the transmissible spongiform encephalopathies or prion diseases. Chapter 8 focuses on human prion disorders, their history, etiology, symptoms, and the therapeutic strategies tried so far. The unusual properties of prion propagation have presented challenges to researchers seeking to understandthe pathogenic mechanisms of these diseases. Chapter 9 is aimed to provide evidence on the impact of abusing drugs on cognitive functions. The author shows that most drugs of abuse can induce adverse effects which seem to impact brain circuits linked to important aspects of cognition, such as memory and learning, attention, risk taking, motivation, mood and wanting. Possible approaches to deal with this drug-induced damage from the pharmacological point of view are also discussed. [...]... require follow up and management of their handicaps: regimens to do this have been 16 Brain Damage – Bridging Between Basic Research and Clinics described (Robertson & Perlman 2006) Outcome prediction for infants with HIE has been proposed using defined periods (0-6 hours after birth, 6-72 hours after birth, and before discharge) and clinical, imaging and electrophysiological predictors, and neurological... unexplained 4 Brain Damage – Bridging Between Basic Research and Clinics stillbirth An infant born with evidence of brain injury potentially due to a genetic cause requires chromosome studies, placental pathology, and family evaluation in addition to radiological and general and often specific laboratory studies Prognosis varies; some genetic syndromes are invariably fatal while the spectrum for brain involvement,... fetal brain and neurological system are anticonvulsant medications and cancer therapies (Halopainen & Lauren 2011) But, while there is general recognition that any medication should be considered carefully in the context of pregnancy and wherever possible be discontinued, in some instances the wellbeing of the mother has to be weighed against the 8 Brain Damage – Bridging Between Basic Research and Clinics. .. permanent sequelae and may be underreported (Ozduman et al 2004) The overall incidence of cerebral palsy has not been reduced significantly in spite of advances in obstetric care, and CP remains a significant cause for motor deficits and cognitive disability that become evident in early life and result in permanent disability 2 Brain Damage – Bridging Between Basic Research and Clinics Hypoxia is... key issues to avoid brain injury in infants presenting by the breech (bottom first – or with the part normally covered by the britches presenting) are assistance 22 Brain Damage – Bridging Between Basic Research and Clinics during delivery to protect the after coming head and the attendance of staff to effectively resuscitate the infant, who in many instances is born prematurely and after a degree of... may still occur to some degree but is usually mild or absent 12 Brain Damage – Bridging Between Basic Research and Clinics A recent review identified 5 sub-patterns of acute near total injury (Okereafor et al 2008) In pattern 1, basal ganglia and thalami lesions were associated with severe white matter damage; pattern 2 had basal ganglia and thalami lesions with mild or moderate white matter changes;... Predisposing factors for fetal brain injury Prematurity: Brain injury in the premature infant is an extremely important problem, in part because of the large absolute number of infants affected yearly (Volpe 1997) Considerable 6 Brain Damage – Bridging Between Basic Research and Clinics research documents that children born very prematurely ( . BRAIN DAMAGE – BRIDGING BETWEEN BASIC RESEARCH AND CLINICS Edited by Alina González-Quevedo Brain Damage – Bridging Between Basic Research and Clinics Edited. cause for motor deficits and cognitive disability that become evident in early life and result in permanent disability. Brain Damage – Bridging Between Basic Research and Clinics 2 Hypoxia. (Volpe 1997) Considerable Brain Damage – Bridging Between Basic Research and Clinics 6 research documents that children born very prematurely (<32 weeks gestation) and or/extremely low birth