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




Mechanisms of Neuroinflammation


Book Description

"Mechanisms of Neuroinflammation" book explains how the neuronal cells become swollen at the moment of the blood-brain barrier disruption and how they lose their immunological isolation. A cascade of cytokines and immune cells from the bloodstream enters the nervous system, inflaming neurons and activating the glia. This produces a neuroinflammatory process that can generate different neurodegenerative diseases. Better understanding of mechanisms that are activated at the time when the damage to the brain occurs could lead to the development of suitable therapies that revert the neuronal inflammation and thus prevent further damage to the nervous system.




Mechanisms of Neuroinflammation and Inflammatory Neurodegeneration in Acute Brain Injury


Book Description

Mechanisms of brain-immune interactions became a cutting-edge topic in systemic neurosciences over the past years. Acute lesions of the brain parenchyma, particularly, induce a profound and highly complex neuroinflammatory reaction with similar mechanistic properties between differing disease paradigms like ischemic stroke, intracerebral hemorrhage (ICH) and traumatic brain injury (TBI). Resident microglial cells sense tissue damage and initiate inflammation, activation of the endothelial brain-immune interface promotes recruitment of systemic immune cells to the brain and systemic humoral immune mediators (e.g. complements and cytokines) enter the brain through the damaged blood-brain barrier. These cellular and humoral constituents of the neuroinflammatory reaction to brain injury contribute substantially to secondary brain damage and neurodegeneration. Diverse inflammatory cascades such as pro-inflammatory cytokine secretion of invading leukocytes and direct cell-cell-contact cytotoxicity between lymphocytes and neurons have been demonstrated to mediate the inflammatory ‘collateral damage’ in models of acute brain injury. Besides mediating neuronal cell loss and degeneration, secondary inflammatory mechanisms also contribute to functional modulation of neurons and the impact of post-lesional neuroinflammation can even be detected on the behavioral level. The contribution of several specific immune cell subpopulations to the complex orchestration of secondary neuroinflammation has been revealed just recently. However, the differential vulnerability of specific neuronal cell types and the molecular mechanisms of inflammatory neurodegeneration are still elusive. Furthermore, we are only on the verge of characterizing the control of long-term recovery and neuronal plasticity after brain damage by inflammatory pathways. Yet, a more detailed but also comprehensive understanding of the multifaceted interaction of these two supersystems is of direct translational relevance. Immunotherapeutic strategies currently shift to the center of translational research in acute CNS lesion since all clinical trials investigating direct neuroprotective therapies failed. To advance our knowledge on brain-immune communications after brain damage an interdisciplinary approach covered by cellular neuroscience as well as neuroimmunology, brain imaging and behavioral sciences is crucial to thoroughly depict the intricate mechanisms.




Neuroinflammation


Book Description

Inflammation is a central mechanism in many neurological diseases, including stroke, multiple sclerosis, and brain trauma as well as meningitis and contributes to the generation of pain. We are now beginning to understand the impact of the immune system on different nervous system functions and diseases, ranging from damage through tolerance to modulation and repair.This book discusses some of the more common neuro-inflammatory diseases. Topics covered include multiple sclerosis, optic neuritis and Susac syndrome. - Comprehensive review of the latest developments in neuroinflammation - Includes contributions from leading authorities




Brain Neurotrauma


Book Description

With the contribution from more than one hundred CNS neurotrauma experts, this book provides a comprehensive and up-to-date account on the latest developments in the area of neurotrauma including biomarker studies, experimental models, diagnostic methods, and neurotherapeutic intervention strategies in brain injury research. It discusses neurotrauma mechanisms, biomarker discovery, and neurocognitive and neurobehavioral deficits. Also included are medical interventions and recent neurotherapeutics used in the area of brain injury that have been translated to the area of rehabilitation research. In addition, a section is devoted to models of milder CNS injury, including sports injuries.




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”.




Animal Models of Acute Neurological Injuries


Book Description

Despite numerous recent studies and exciting discoveries in the field, only limited treatment is available today for the victims of acute neurological injuries. Animal Models of Acute Neurological Injuries provides a standardized methodology manual designed to eliminate the inconsistent preparations and variability that currently jeopardizes advances in the field. Contributed by top experts and many original developers of the models, each chapter contains a step-by-step, proven procedure and visual aids covering the most commonly used animal models of neurological injury in order to highlight the practical applications of animal models rather than the theoretical issues. This intensive volume presents its readily reproducible protocols with great clarity and consistency to best aid neuroscientists and neurobiologists in laboratory testing and experimentation. Comprehensive and cutting-edge, Animal Models of Acute Neurological Injuries is an ideal guide for scientists and researchers who wish to pursue this vital course of study with the proficiency and precision that the field requires.




Neuroinflammation in Stroke


Book Description

The successful treatment of acute stroke remains one of the major challenges in clinical medicine. Over the last decades, the understanding of stroke pathophysiology has greatly improved, while the therapeutic options in stroke therapy remain very limited. Today, hyperacute mechanisms of damage, such as excitotoxicity, can be discriminated from delayed ones, such as inflammation and apoptosis. Targeting of inflammation has already been successfully applied in various stroke models, but translation into a clinically efficacious strategy has not been achieved so far. In this book, leading experts in basic cerebrovascular research as well as stroke treatment review the current evidence for and against an important role for inflammation in stroke, and explore the potential of treating or modulating inflammation in stroke therapy.




The Neurobiology of Multiple Sclerosis


Book Description

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disorder of the human central nervous system (CNS) which usually affects young adults with certain genetic backgrounds who are then exposed to certain precipitating environmental antigen(s). Despite major advances of the past two decades in understanding the pathophysiology of MS, and in spite of the introduction of new immunomodulatory and immuno-suppressive agents which may slow down disease progression and delay the onset of disability, the "cause and the "cure for MS remain elusive. This volume of International Review of Neurobiology focuses on MS and related disorders. The volume can be divided into various sections with the main emphasis on MS pathogenesis, clinical features and epidemiology, neuroimaging, and treatment. The ultimate goal of this book is to encourage further research into the pathogenesis of this elusive disease.




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.