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Shock (Augusta, Ga.) Jun 2021Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma... (Review)
Review
Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma patients. This phenomenon is initiated by systemic injury to the vascular endothelium that is exacerbated by hypoperfusion, acidosis, and hypothermia and leads to systemic activation of the coagulation cascades and resultant coagulopathy. Many previous studies have focused on endotheliopathy with targeted markers such as syndecan-1, soluble thrombomodulin, and plasma adrenaline as potential culprits for initiation and propagation of this state. However, in more recent studies, hyperadhesive von Willebrand factor (VWF), which is released following endothelial injury, and its cleaving metalloprotease ADAMTS13 have emerged as significant targets of the downstream effect of endothelial breakdown and coagulation dysregulation. Elucidation of the mechanism by which the dysregulated VWF-ADAMTS13 axis leads to endothelial dysfunction and coagulopathy after trauma can help identify new targets for therapy and sites for intervention. Much of what is known mechanistically regarding VWF stems from work done in traumatic brain injury. Following localized brain injury, brain-derived extracellular vesicles are released into circulation where they induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. VWF released from injured endothelial cells binds to these extracellular vesicles to enhance their activity in promoting coagulopathy and increasing endothelial permeability. However, there are numerous gaps in our knowledge of VWF following injury, providing a platform for further investigation.
Topics: Blood Coagulation Disorders; Brain Injuries, Traumatic; Humans; Wounds and Injuries; von Willebrand Factor
PubMed: 33156241
DOI: 10.1097/SHK.0000000000001690 -
Stem Cell Reviews and Reports Aug 2021Traumatic injuries are a leading cause of death and disability in both military and civilian populations. Given the complexity and diversity of traumatic injuries, novel... (Review)
Review
Traumatic injuries are a leading cause of death and disability in both military and civilian populations. Given the complexity and diversity of traumatic injuries, novel and individualized treatment strategies are required to optimize outcomes. Cellular therapies have potential benefit for the treatment of acute or chronic injuries, and various cell-based pharmaceuticals are currently being tested in preclinical studies or in clinical trials. Cellular therapeutics may have the ability to complement existing therapies, especially in restoring organ function lost due to tissue disruption, prolonged hypoxia or inflammatory damage. In this article we highlight the current status and discuss future directions of cellular therapies for the treatment of traumatic injury. Both published research and ongoing clinical trials are discussed here.
Topics: Cell- and Tissue-Based Therapy; Humans; Wounds and Injuries
PubMed: 33420590
DOI: 10.1007/s12015-020-10086-7 -
Blood Aug 2016Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant... (Review)
Review
Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be "normal" after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.
Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Brain Injuries, Traumatic; Humans; Models, Biological; Wounds and Injuries
PubMed: 27381903
DOI: 10.1182/blood-2016-01-636423 -
Journal of Translational Medicine Jun 2011Trauma is one of the leading causes of death in young adult patients. Many pre-clinical and clinical studies attempt to investigate the immunological pathways involved,... (Review)
Review
BACKGROUND
Trauma is one of the leading causes of death in young adult patients. Many pre-clinical and clinical studies attempt to investigate the immunological pathways involved, however the true mediators remain to be elucidated. Herein, we attempt to describe the immunologic response to systemic trauma in the context of the Danger model.
DATA SOURCES
A literature search using PubMed was used to identify pertinent articles describing the Danger model in relation to trauma.
CONCLUSIONS
Our knowledge of Danger signals in relation to traumatic injury is still limited. Danger/alarmin signals are the most proximal molecules in the immune response that have many possibilities for effector function in the innate and acquired immune systems. Having a full understanding of these molecules and their pathways would give us the ability to intervene at such an early stage and may prove to be more effective in blunting the post-injury inflammatory response unlike previously failed cytokine experiments.
Topics: Humans; Models, Biological; Signal Transduction; Wounds and Injuries
PubMed: 21676213
DOI: 10.1186/1479-5876-9-92 -
FEBS Letters Jun 2015The nervous system plays critical roles in the stress response. Animals can survive and function under harsh conditions, and resist and recover from injuries because... (Review)
Review
The nervous system plays critical roles in the stress response. Animals can survive and function under harsh conditions, and resist and recover from injuries because neurons perceive and respond to various stressors through specific regulatory mechanisms. Caenorhabditis elegans has served as an excellent model to discover fundamental mechanisms underlying the neuronal response to stress. The basic physiological processes that C. elegans exhibits under stress conditions are similar to those observed in higher organisms. Many molecular pathways activated by environmental and cellular stresses are also conserved. In this review, we summarize major findings in examining neuronal responses to hypoxia, oxidative stress, osmotic stress, and traumatic injury. These studies from C. elegans have provided novel insights into our understanding of neuronal responses to stress at the molecular, cellular, and circuit levels.
Topics: Animals; Caenorhabditis elegans; Neurons; Osmotic Pressure; Oxidative Stress; Stress, Physiological; Wounds and Injuries
PubMed: 25979176
DOI: 10.1016/j.febslet.2015.05.005 -
BMC Neurology Oct 2004Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized. (Comparative Study)
Comparative Study
BACKGROUND
Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized.
METHODS
Specific information was obtained from the medical records of 15 consecutive patients with chronic headaches related to physically injurious traumatic events that did not include either head trauma or whiplash injury. The events and the physical injuries produced by them were noted. The headaches' development, characteristics, duration, frequency, and accompaniments were recorded, as were the patients' use of pain-alleviative drugs. From this latter information, the headaches were classified by the diagnostic criteria of the International Headache Society as though they were naturally-occurring headaches. The presence of other post-traumatic symptoms and litigation were also recorded.
RESULTS
The intervals between the events and the onset of the headaches resembled those between head traumas or whiplash injuries and their subsequent headaches. The headaches themselves were, as a group, similar to those after head trauma and whiplash injury. Thirteen of the patients had chronic tension-type headache, two had migraine. The sustained bodily injuries were trivial or unidentifiable in nine patients. Fabrication of symptoms for financial remuneration was not evident in these patients of whom seven were not even seeking payments of any kind.
CONCLUSIONS
This study suggests that these hitherto unrecognized post-traumatic headaches constitute a class of headaches characterized by a relation to traumatic events affecting the body but not including head or whiplash traumas. The bodily injuries per se can be discounted as the cause of the headaches. So can fabrication of symptoms for financial remuneration. Altered mental states, not systematically evaluated here, were a possible cause of the headaches. The overall resemblance of these headaches to the headaches after head or whiplash traumas implies that these latter two headache types may likewise not be products of structural injuries.
Topics: Adult; Chronic Disease; Craniocerebral Trauma; Female; Headache; Humans; Male; Middle Aged; Whiplash Injuries; Wounds and Injuries
PubMed: 15516263
DOI: 10.1186/1471-2377-4-17 -
Anaesthesia Dec 2017
Topics: Fluid Therapy; Hemorrhage; Humans; Hypotension; Wounds and Injuries
PubMed: 28940420
DOI: 10.1111/anae.14034 -
Military Medical Research Oct 2018Despite efforts in prevention and intensive care, trauma and subsequent sepsis are still associated with a high mortality rate. Traumatic injury remains the main cause... (Review)
Review
Despite efforts in prevention and intensive care, trauma and subsequent sepsis are still associated with a high mortality rate. Traumatic injury remains the main cause of death in people younger than 45 years and is thus a source of immense social and economic burden. In recent years, the knowledge concerning gender medicine has continuously increased. A number of studies have reported gender dimorphism in terms of response to trauma, shock and sepsis. However, the advantageous outcome following trauma-hemorrhage in females is not due only to sex. Rather, it is due to the prevailing hormonal milieu of the victim. In this respect, various experimental and clinical studies have demonstrated beneficial effects of estrogen for the central nervous system, the cardiopulmonary system, the liver, the kidneys, the immune system, and for the overall survival of the host. Nonetheless, there remains a gap between the bench and the bedside. This is most likely because clinical studies have not accounted for the estrus cycle. This review attempts to provide an overview of the current level of knowledge and highlights the most important organ systems responding to trauma, shock and sepsis. There continues to be a need for clinical studies on the prevailing hormonal milieu following trauma, shock and sepsis.
Topics: Animals; Estrogens; Female; Hemorrhage; Humans; Immune System; Male; Multiple Organ Failure; Sepsis; Sex Characteristics; Shock, Traumatic; Wounds and Injuries
PubMed: 30360757
DOI: 10.1186/s40779-018-0182-5 -
Acta Biochimica Et Biophysica Sinica Sep 2015Traumatic injury is a leading cause of mortality and morbidity. MicroRNAs (miRNAs) regulate the cellular responses when traumatic injury occurs. Previously, we reported...
Traumatic injury is a leading cause of mortality and morbidity. MicroRNAs (miRNAs) regulate the cellular responses when traumatic injury occurs. Previously, we reported that miR-3945, miR-125a-5p, miR-363-3p, and miR-150-5p were significantly altered in neutrophils of patients who suffered traumatic injury. In the present study, by comparing neutrophils of patients suffering from major trauma with neutrophils of patients with a inflammatory disease, we found that the variation trend of miR-150-5p was relatively different in the process of these two diseases. Gene Ontology and pathway analysis of miR-150-5p revealed that it may activate the mitogen-activated protein kinase and Toll-like receptor signaling pathways and cell adhesion molecules when the traumatic injury occurs. In addition, protein kinase C alpha (PRKCA) was also identified as a direct target of miR-150-5p by establishing a miRNA-mRNA network, and this target was validated via dual-luciferase reporter and western blot analysis. Our results suggested that the expression of miR-150-5p was down-regulated in neutrophils after a major traumatic injury. miR-150-5p and its identified target PRKCA play important roles in the development of traumatic process.
Topics: Computational Biology; HEK293 Cells; Humans; MicroRNAs; Neutrophils; Protein Kinase C-alpha; Wounds and Injuries
PubMed: 26232986
DOI: 10.1093/abbs/gmv072 -
International Journal of Molecular... Sep 2020Despite advances in treatment and care, burn trauma remains the fourth most common type of traumatic injury. Burn-induced cardiac failure is a key factor for patient... (Review)
Review
Despite advances in treatment and care, burn trauma remains the fourth most common type of traumatic injury. Burn-induced cardiac failure is a key factor for patient mortality, especially during the initial post-burn period (the first 24 to 48 h). Mitochondria, among the most important subcellular organelles in cardiomyocytes, are a central player in determining the severity of myocardial damage. Defects in mitochondrial function and structure are involved in pathogenesis of numerous myocardial injuries and cardiovascular diseases. In this article, we comprehensively review the current findings on cardiac mitochondrial pathological changes and summarize burn-impaired mitochondrial respiration capacity and energy supply, induced mitochondrial oxidative stress, and increased cell death. The molecular mechanisms underlying these alterations are discussed, along with the possible influence of other biological variables. We hope this review will provide useful information to explore potential therapeutic approaches that target mitochondria for cardiac protection following burn injury.
Topics: Animals; Burns; Humans; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Wounds and Injuries
PubMed: 32932869
DOI: 10.3390/ijms21186655