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Neurochemical Research Dec 2015Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and... (Review)
Review
Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed.
Topics: Adult; Animals; Brain; Brain Chemistry; Brain Injuries; Energy Metabolism; Female; Humans; Infant, Premature, Diseases; Pregnancy
PubMed: 26148530
DOI: 10.1007/s11064-015-1600-7 -
Journal of Osteopathic Medicine Jan 2023Across all segments of society in the United States, millions of adults and children experience a traumatic brain injury (TBI) each year, which may pose lifetime health...
Across all segments of society in the United States, millions of adults and children experience a traumatic brain injury (TBI) each year, which may pose lifetime health and financial burdens in the billions of dollars. Efforts have been made to advance research and care with goals to improve awareness of the causes and consequences of TBI, but gaps still remain in understanding TBI and delivering high-quality care to everyone who needs it both in military and civilian life. At the request of the Department of Defense, the National Academies of Sciences, Engineering and Medicine recently convened experts to address existing gaps in brain injury science and systems of care. Although many people who experience a TBI recover fully, others experience long-term physical, emotional, and often financial consequences to the patient and family system, and require ongoing accommodations to support their return to the communities in which they live, learn, and work. A holistic approach within the context of osteopathic medicine may be helpful and enhance contributions within the field. This article will discuss the roadmap to help guide the field, including key conclusions and recommendations for actions to advance progress over the next decade while embracing a comprehensive bio-psycho-socio-ecological model of TBI care bringing in the distinctive osteopathic approach not only to improve care and outcomes, but also to understand patient and family experiences on their TBI journey.
Topics: Adult; Child; Humans; United States; Brain Injuries, Traumatic; Emotions
PubMed: 36039523
DOI: 10.1515/jom-2022-0154 -
International Journal of Molecular... Sep 2023Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually.... (Review)
Review
Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds. HBOT consists of 100% oxygen administration, usually between 1.5 and 3 atm and has been found to increase brain oxygenation levels after hypoxia in addition to decreasing levels of inflammation, apoptosis, intracranial pressure, and edema, reducing subsequent secondary injury. The following review examines recent preclinical and clinical studies on HBOT in the context of TBI with a focus on contributing mechanisms and clinical potential. Several preclinical studies have identified pathways, such as TLR4/NF-kB, that are affected by HBOT and contribute to its therapeutic effect. Thus far, the mechanisms mediating HBOT treatment have yet to be fully elucidated and are of interest to researchers. Nonetheless, multiple clinical studies presented in this review have examined the safety of HBOT and demonstrated the improved neurological function of TBI patients after HBOT, deeming it a promising avenue for treatment.
Topics: Humans; Hyperbaric Oxygenation; Brain Injuries, Traumatic; Brain Injuries; Brain; Oxygen
PubMed: 37834059
DOI: 10.3390/ijms241914612 -
Pediatric Neurology Apr 2022Children with acute neurologic illness are at high risk of mortality and long-term neurologic disability. Severe traumatic brain injury, cardiac arrest, stroke, and... (Review)
Review
Children with acute neurologic illness are at high risk of mortality and long-term neurologic disability. Severe traumatic brain injury, cardiac arrest, stroke, and central nervous system infection are often complicated by cerebral hypoxia, hypoperfusion, and edema, leading to secondary neurologic injury and worse outcome. Owing to the paucity of targeted neuroprotective therapies for these conditions, management emphasizes close physiologic monitoring and supportive care. In this review, we will discuss advanced neurologic monitoring strategies in pediatric acute neurologic illness, emphasizing the physiologic concepts underlying each tool. We will also highlight recent innovations including novel monitoring modalities, and the application of neurologic monitoring in critically ill patients at risk of developing neurologic sequelae.
Topics: Brain Injuries; Brain Injuries, Traumatic; Child; Critical Care; Critical Illness; Heart Arrest; Humans; Monitoring, Physiologic
PubMed: 35240364
DOI: 10.1016/j.pediatrneurol.2022.01.006 -
Science (New York, N.Y.) Aug 2016Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells.... (Review)
Review
Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed.
Topics: Animals; Brain Injuries; Disease Models, Animal; Humans; Inflammation; Myeloid Cells; Neuroprotection
PubMed: 27540166
DOI: 10.1126/science.aaf6260 -
Seminars in Neurology Feb 2015Moderate and severe traumatic brain injury (TBI) is the leading cause of morbidity and mortality among young individuals in high-income countries. Its pathophysiology is... (Review)
Review
Moderate and severe traumatic brain injury (TBI) is the leading cause of morbidity and mortality among young individuals in high-income countries. Its pathophysiology is divided into two major phases: the initial neuronal injury (or primary injury) followed by secondary insults (secondary injury). Multimodality monitoring now offers neurointensivists the ability to monitor multiple physiologic parameters that act as surrogates of brain ischemia and hypoxia, the major driving forces behind secondary brain injury. The heterogeneity of the pathophysiology of TBI makes it necessary to take into consideration these interacting physiologic factors when recommending for or against any therapies; it may also account for the failure of all the neuroprotective therapies studied so far. In this review, the authors focus on neuroclinicians and neurointensivists, and discuss the developments in therapeutic strategies aimed at optimizing intracranial pressure and cerebral perfusion pressure, and minimizing cerebral hypoxia. The management of moderate to severe TBI in the intensive care unit is moving away from a pure "threshold-based" treatment approach toward consideration of patient-specific characteristics, including the state of cerebral autoregulation. The authors also include a concise discussion on the management of medical and neurologic complications peculiar to TBI as well as an overview of prognostication.
Topics: Brain Injuries; Disease Management; Humans; Intensive Care Units
PubMed: 25714866
DOI: 10.1055/s-0035-1544238 -
Behavioural Neurology 2016Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show... (Review)
Review
Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD.
Topics: Animals; Autistic Disorder; Brain; Brain Injuries; Brain Injuries, Traumatic; Humans; Pediatrics; Practice Guidelines as Topic
PubMed: 28074078
DOI: 10.1155/2016/8781725 -
Seminars in Neurology Feb 2015Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition... (Review)
Review
Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discussTBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field.
Topics: Brain Injuries; Emergency Treatment; Humans
PubMed: 25714870
DOI: 10.1055/s-0035-1544237 -
Neuron Dec 2012The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and... (Review)
Review
The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE.
Topics: Amyloid beta-Peptides; Animals; Brain; Brain Injuries; DNA-Binding Proteins; Humans; Neurobiology; Neurodegenerative Diseases; Neurons; tau Proteins
PubMed: 23217738
DOI: 10.1016/j.neuron.2012.11.021 -
BMC Neurology Dec 2023The brain is the control centre of the human body. Injury to the brain can have diverse and disabling effects. Yet there remain important unanswered questions for...
The brain is the control centre of the human body. Injury to the brain can have diverse and disabling effects. Yet there remain important unanswered questions for clinicians, those affected and their families. This special collection aims to advance understanding of how we can better diagnose, treat and support those affected by brain injury across the severity spectrum.
Topics: Humans; Brain Injuries, Traumatic; Brain Injuries; Brain
PubMed: 38082269
DOI: 10.1186/s12883-023-03484-0