Brain Injury as a Neurodegenerative Disorder


Book Description

It has been long assumed that following the resolution of acute injuries, traumatic brain injury represents a stable neural entity. However, there is growing evidence that a single moderate-severe brain injury may instead trigger an ongoing deteriorative process that commences sub-acutely, and occurs regardless of age. For scientists and clinicians, it is critical to examine this body of evidence and to explore its implications. Do the findings represent a neurodegenerative process or can they be alternatively explained? What are the neural, behavioural and functional characteristics of this progressive deterioration? Such information is needed to develop treatments to prevent or mitigate decline, and to inform the clinical care of brain injured patients. Research and clinical practice are influenced by the assumption that moderate-severe TBI is non-progressive, with few studies exploring treatments to prevent progression, and rehabilitation typically concentrated in the early stages of injury. Brain injuries can never be fully prevented. However, understanding that such progressive deterioration occurs opens a novel area of research - prevention of secondary decline - offering new possibilities for the improvement of long-term outcomes in people with traumatic brain injury.




Handbook of Traumatic Brain Injury and Neurodegeneration


Book Description

Holbourne’s theory that rotational head movement and shear strains were limiting factors in producing acute parenchymal brain damage was a watershed moment in understanding traumatic brain injury (TBI). Long term effects, and in particular neurodegenerative proteinopathy subsequent to TBI, remain theoretical, notwithstanding the poorly understood ‘punch drunk’ syndrome of the early and mid-20th century, and the 21st century concept of chronic traumatic encephalopathy. This book, the Handbook of Traumatic Brain Injury and Neurodegeneration, has as its theme the marriage between neurodegenerative disease and neurotrauma through TBI surrogates such as sport, military service, and experimental models, and the legitimacy of that marriage. In the 32 contributions included here, this handbook not only explores the deleterious effects of genuine TBI, but also, and more importantly, the relationship between TBI and neurodegeneration. Controversy notwithstanding, there is much to be learned about the biological effects of TBI, substrates for long-term sequelae, the relationship between TBI and diverse neuropsychiatric disorders, and targets for therapy. The overall message to the neuroscience community from these papers may be a cautionary tale. The null hypothesis, that there is no causal relationship between TBI and progressive neurodegenerative disease, appears to be very much in play, and the book will be of interest to all those working in the field.




Brain Injury as a Neurodegenerative Disorder


Book Description

It has been long assumed that following the resolution of acute injuries, traumatic brain injury represents a stable neural entity. However, there is growing evidence that a single moderate-severe brain injury may instead trigger an ongoing deteriorative process that commences sub-acutely, and occurs regardless of age. For scientists and clinicians, it is critical to examine this body of evidence and to explore its implications. Do the findings represent a neurodegenerative process or can they be alternatively explained? What are the neural, behavioural and functional characteristics of this progressive deterioration? Such information is needed to develop treatments to prevent or mitigate decline, and to inform the clinical care of brain injured patients. Research and clinical practice are influenced by the assumption that moderate-severe TBI is non-progressive, with few studies exploring treatments to prevent progression, and rehabilitation typically concentrated in the early stages of injury. Brain injuries can never be fully prevented. However, understanding that such progressive deterioration occurs opens a novel area of research - prevention of secondary decline - offering new possibilities for the improvement of long-term outcomes in people with traumatic brain injury.




Tau oligomers


Book Description

Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.




Translational Research in Traumatic Brain Injury


Book Description

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme




Biomarkers of Brain Injury and Neurological Disorders


Book Description

This book explores the recent advances in the techniques and platforms used in biomarker research that have revolutionized the way we study, diagnose, and treat brain injury conditions. The contributors describe different biomarker studies pertaining to brain injury and other neurological disorders and analyze the different models and technologies




Invisible Wounds of War


Book Description

Since October 2001, approximately 1.64 million U.S. troops have been deployed for Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) in Afghanistan and Iraq. Early evidence suggests that the psychological toll of these deployments -- many involving prolonged exposure to combat-related stress over multiple rotations -- may be disproportionately high compared with the physical injuries of combat. In the face of mounting public concern over post-deployment health care issues confronting OEF/OIF veterans, several task forces, independent review groups, and a Presidential Commission have been convened to examine the care of the war wounded and make recommendations. Concerns have been most recently centered on two combat-related injuries in particular: post-traumatic stress disorder and traumatic brain injury. With the increasing incidence of suicide and suicide attempts among returning veterans, concern about depression is also on the rise. The study discussed in this monograph focuses on post-traumatic stress disorder, major depression, and traumatic brain injury, not only because of current high-level policy interest but also because, unlike the physical wounds of war, these conditions are often invisible to the eye, remaining invisible to other servicemembers, family members, and society in general. All three conditions affect mood, thoughts, and behavior; yet these wounds often go unrecognized and unacknowledged. The effect of traumatic brain injury is still poorly understood, leaving a large gap in knowledge related to how extensive the problem is or how to address it. RAND conducted a comprehensive study of the post-deployment health-related needs associated with these three conditions among OEF/OIF veterans, the health care system in place to meet those needs, gaps in the care system, and the costs associated with these conditions and with providing quality health care to all those in need. This monograph presents the results of our study, which should be of interest to mental health treatment providers; health policymakers, particularly those charged with caring for our nation's veterans; and U.S. service men and women, their families, and the concerned public. All the research products from this study are available at http://veterans.rand.org. Data collection for this study began in April 2007and concluded in January 2008. Specific activities included a critical reviewof the extant literature on the prevalence of post-traumatic stress disorder, major depression, and traumatic brain injury and their short- and long-term consequences; a population-based survey of service members and veterans who served in Afghanistan or Iraq to assess health status and symptoms, as well asutilization of and barriers to care; a review of existing programs to treat service members and veterans with the three conditions; focus groups withmilitary service members and their spouses; and the development of a microsimulation model to forecast the economic costs of these conditions overtime. Among our recommendations is that effective treatments documented in the scientific literature -- evidence-based care -- are available for PTSD and major depression. Delivery of such care to all veterans with PTSD or majordepression would pay for itself within two years, or even save money, by improving productivity and reducing medical and mortality costs. Such care may also be a cost-effective way to retain a ready and healthy military force for the future. However, to ensure that this care is delivered requires system-level changes across the Department of Defense, the Department of Veterans Affairs, and the U.S. health care system.




Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases


Book Description

Collectively, neurodegenerative diseases are characterized by chronic and progressive loss of neurons in discrete areas of the brain, producing debilitating symptoms such as dementia, loss of memory, loss of sensory or motor capability, decreased overall quality of life eventually leading to premature death. Two types of cell death are known to occur during neurodegeneration: (a) apoptosis and (b) necrosis. The necrosis is characterized by the passive cell swelling, intense mitochondrial damage with rapid loss of ATP, alterations in neural membrane permeability, high calcium influx, and disruption of ion homeostasis. This type of cell death leads to membrane lysis and release of intracellular components that induce inflammatory reactions. Necrotic cell death normally occurs at the core of injury site. In contrast, apoptosis is an active process in which caspases (a group of endoproteases with specificity for aspartate residues in protein) are stimulated. Apoptotic cell death is accompanied by cell shrinkage, dynamic membrane blebbing, chromatin condensation, DNA laddering, loss of phospholipids asymmetry, low ATP levels, and mild calcium overload. This type of cell death normally occurs in penumbral region at the ischemic injury site and in different regions in various neurodegenerative diseases.




Sports-Related Concussions in Youth


Book Description

In the past decade, few subjects at the intersection of medicine and sports have generated as much public interest as sports-related concussions - especially among youth. Despite growing awareness of sports-related concussions and campaigns to educate athletes, coaches, physicians, and parents of young athletes about concussion recognition and management, confusion and controversy persist in many areas. Currently, diagnosis is based primarily on the symptoms reported by the individual rather than on objective diagnostic markers, and there is little empirical evidence for the optimal degree and duration of physical rest needed to promote recovery or the best timing and approach for returning to full physical activity. Sports-Related Concussions in Youth: Improving the Science, Changing the Culture reviews the science of sports-related concussions in youth from elementary school through young adulthood, as well as in military personnel and their dependents. This report recommends actions that can be taken by a range of audiences - including research funding agencies, legislatures, state and school superintendents and athletic directors, military organizations, and equipment manufacturers, as well as youth who participate in sports and their parents - to improve what is known about concussions and to reduce their occurrence. Sports-Related Concussions in Youth finds that while some studies provide useful information, much remains unknown about the extent of concussions in youth; how to diagnose, manage, and prevent concussions; and the short- and long-term consequences of concussions as well as repetitive head impacts that do not result in concussion symptoms. The culture of sports negatively influences athletes' self-reporting of concussion symptoms and their adherence to return-to-play guidance. Athletes, their teammates, and, in some cases, coaches and parents may not fully appreciate the health threats posed by concussions. Similarly, military recruits are immersed in a culture that includes devotion to duty and service before self, and the critical nature of concussions may often go unheeded. According to Sports-Related Concussions in Youth, if the youth sports community can adopt the belief that concussions are serious injuries and emphasize care for players with concussions until they are fully recovered, then the culture in which these athletes perform and compete will become much safer. Improving understanding of the extent, causes, effects, and prevention of sports-related concussions is vitally important for the health and well-being of youth athletes. The findings and recommendations in this report set a direction for research to reach this goal.




Brain Damage and Repair


Book Description

This book builds a novel bridge from molecular research to clinical therapy. This approach reveals the functional features of neurons and glia in the particular context of vulnerability and self-protection, intracellular properties and extracellular matrix. Arising from this platform, this volume unfolds the molecular and systemic processes underlying migration disorders, axonal injury, repair and regeneration.