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Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. The definition of TBI has not been consistent and tends to vary according to specialties and circumstances. The term brain injury is often used synonymously with head injury, which may not be associated with neurological deficits. The definition has also been problematic due to variations in inclusion criteria. Both American and Brazilian data indicate that more than 700,000 people suffer TBI annually, with 20% afflicted with moderate or severe TBI. According to this data, 80% of people who suffered mild TBI can return to work, whist only 20% of moderate, and 10% of victims of severe TBI can return to their daily routine. Cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions, altered as a result of cerebral injury, is extremely important for these individuals. The aim of a cognitive and motor rehabilitation program is to recover an individual's ability to process, interpret and respond appropriately to environmental inputs, as well as to create strategies and procedures to compensate for lost functions that are necessary in familial, social, educational and occupational relationships. In general, the cognitive rehabilitation programs tend to focus on specific cognitive domains, such as memory, motor, language and executive functions. By contrast, the focus of compensatory training procedures is generally on making environmental adaptations and changes to provide grater autonomy for patients. Successful cognitive rehabilitation programs are those whose aim is both recovery and compensation based on an integrated and interdisciplinary approach. The purpose of this Research Topic is to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in mild, moderate and severe TBI survivors, and the most cognitive and motor impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. Within this context, the importance of an interdisciplinary rehabilitation for TBI is underlined.

Traumatic Brain Injury --- Diffuse Axonal Injury --- concussion --- cognitive impairment

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Concussion --- traumatic brain injury --- treatment --- rehabilitation --- clinical trials

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Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. The definition of TBI has not been consistent and tends to vary according to specialties and circumstances. The term brain injury is often used synonymously with head injury, which may not be associated with neurological deficits. The definition has also been problematic due to variations in inclusion criteria. Both American and Brazilian data indicate that more than 700,000 people suffer TBI annually, with 20% afflicted with moderate or severe TBI. According to this data, 80% of people who suffered mild TBI can return to work, whist only 20% of moderate, and 10% of victims of severe TBI can return to their daily routine. Cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions, altered as a result of cerebral injury, is extremely important for these individuals. The aim of a cognitive and motor rehabilitation program is to recover an individual's ability to process, interpret and respond appropriately to environmental inputs, as well as to create strategies and procedures to compensate for lost functions that are necessary in familial, social, educational and occupational relationships. In general, the cognitive rehabilitation programs tend to focus on specific cognitive domains, such as memory, motor, language and executive functions. By contrast, the focus of compensatory training procedures is generally on making environmental adaptations and changes to provide grater autonomy for patients. Successful cognitive rehabilitation programs are those whose aim is both recovery and compensation based on an integrated and interdisciplinary approach. The purpose of this Research Topic is to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in mild, moderate and severe TBI survivors, and the most cognitive and motor impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. Within this context, the importance of an interdisciplinary rehabilitation for TBI is underlined.

Traumatic Brain Injury --- Diffuse Axonal Injury --- concussion --- cognitive impairment

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Traumatic brain injury (TBI) is a major cause of death and disability and one of the greatest unmet needs in medicine and public health. TBI not only has devastating effects on patients and their relatives but results in huge direct and indirect costs to society. Although guidelines for the management of patients have been developed and more than 200 clinical trials have been conducted, they have resulted in few improvements in clinical outcomes and no effective therapies approved for TBI. It is now apparent that the heterogeneity of clinical TBI is underlain by molecular phenotypes more complex and interactive than initially conceived and current approaches to the characterization, management and outcome prediction of TBI are antiquated, unidimensional and inadequate to capture the interindividual pathophysiological heterogeneity. Recent advances in proteomics and biomarker development provide unparalleled opportunities for unraveling substantial injury-specific and patient-specific variability and refining disease characterization. The identification of novel, sensitive, objective tools, referred to as biomarkers, can revolutionize pathophysiological insights, enable targeted therapies and personalized approaches to clinical management. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. Finally, suggestions are provided for the way forward, with an emphasis on need for a multidimensional approach that integrate a panel of pathobiologically diverse biomarkers with clinical variables and imaging-based assessments to improve diagnosis and classification of TBI and to develop best clinical practice guidelines.

Brain damage. --- Biochemical markers. --- Traumatic Brain Injury --- Brain Injury --- discovery --- clinical practice --- biomarker

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It is now well appreciated that the immune system, in addition to its traditional role in defending the organism against pathogens, communicate in a well-organized fashion with the brain to maintain homeostasis and regulate a set of neural functions. Perturbation in this brain-immune interactions due to inflammatory responses may lead to psychiatric and neurological disorders. Microglia are one of the essential cells involved in the brain-immune interactions. Microglial cells are now not simply regarded as resident tissue macrophages in the brain. These cells are derived from myeloid progenitor cells in the yolk sac in early gestation, travel to the brain parenchyma and interact actively with neurons during the critical period of neurogenesis. Microglia provide a trophic support to developing neurons and take part in the neural wiring through the activity-dependent synapse elimination via direct neuron-microglia interactions. Altered microglial functions including changes in the gene expression due to early life inflammatory events or psychological and environmental stressors can be causally related to neurodevelopmental diseases and mental health disorders. This type of alterations in the neural functions can occur in the absence of infiltration of inflammatory cells in the brain parenchyma or leptomeninges. In this sense, the pathogenetic state underlying a significant part of psychiatric and neurological diseases may be similar to “para-inflammation”, an intermediate state between homeostatic and classical inflammatory states as defined by Ruslan Medzhitov (Nature 454:428-35, 2008). Therefore, it is important to study how systemic inflammation affects brain health and how local peripheral inflammation induces changes in the brain microenvironment. Chronic pain is also induced by disturbance in otherwise well-organized multisystem interplay comprising of reciprocal neural, endocrine and immune interactions. Especially, early-life insults including exposure to immune challenges can alter the neuroanatomical components of nociception, which induces altered pain response later in life. Recently the discrete roles of microglia and blood monocyte-derived macrophages are being defined. The distinction may be further highlighted by disorders in which the brain parenchymal tissue is damaged. Therefore, studies investigating the dynamics of immune cells in traumatic brain injury and neurotropic viral infections including human immunodeficiency virus, etc. as well as neurodegenerative diseases such as amyotrophic lateral sclerosis are promising to clarify the interplay between the central nervous and immune systems. The understanding of the histological architecture providing the infrastructure of such neuro-immune interplay is also essential. This Frontiers research topic brings together fourteen articles and aims to create a platform for researchers in the field of psychoneuroimmunology to share the recent theories, hypotheses and future perspectives regarding open questions on the mechanisms of cell-cell interactions with chemical mediators among the nervous, immune and endocrine systems. We hope that this platform would reveal the relevance of the studies on multisystem interactions to enhance the understanding of the mechanisms underlying a wide variety of neurological and psychiatric disorders.

brain-immune interaction --- fatigue --- pain --- HIV --- neuroinflammation --- traumatic brain injury --- depression --- microglia --- amyotrophic lateral sclerosis --- autism