Expired But Not Yet Dead: Examining the Red Blood Cell Storage Lesion in Extended-Storage Whole Blood.

Whole blood is a powerful resuscitation strategy for trauma patients but has a shorter shelf life than other blood products. The red blood cell storage lesion in whole blood has not previously been investigated beyond the standard storage period. In the present study, we hypothesized that erythrocytes in stored whole blood exhibit similar aspects of the red blood cell storage lesion and that transfusion of extended storage whole blood would not result in a more severe inflammatory response after hemorrhage in a murine model.

Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model.

Introduction: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes.

Innate coagulability changes with age in stored packed red blood cells.

Background: Packed red blood cell (pRBC) units administered during resuscitation from hemorrhagic shock are of varied storage ages. We have previously shown that RBC-derived microparticles' impact on thrombogenesis. However, the impact of storage age on pRBC coagulability is unknown.

Save it-don't waste it! Maximizing utilization of erythrocytes from previously stored whole blood.

Background: Recent military and civilian experience suggests that fresh whole blood may be the preferred for treatment of hemorrhagic shock, but its use is limited by its 21-day shelf life. The red blood cell storage lesion and coagulation status of packed red blood cells (pRBCs) salvaged from expired whole blood are unknown. We hypothesized that pRBCs can be salvaged from previously stored whole blood.

Can Resuscitative Endovascular Balloon Occlusion of the Aorta Fly? Assessing Aortic Balloon Performance for Aeromedical Evacuation.

Background: Noncompressible torso hemorrhage remains a leading cause of death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) placement may occur before transport; however, its efficacy has not been demonstrated at altitude. We hypothesized that changes in altitude would not result in blood pressure changes proximal to a deployed REBOA.

Intrathoracic Pressure Regulator Performance in the Setting of Hemorrhage and Acute Lung Injury.

Introduction: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI).

Oxygenation extremes after traumatic brain injury transiently affect coagulation.

Introduction: Trauma patients may become hypoxic or iatrogenically hyperoxic in the early post-injury period. While both extremes of oxygenation may be harmful following injury, the mechanism has yet to be elucidated. We hypothesized that hypoxia or hyperoxia would induce changes in coagulation, creating a secondary insult exacerbating the primary injury.

Effects of whole blood leukoreduction on platelet function and hemostatic parameters.

Aims/objectives: The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR).

Background: Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern.

UCH-L1 is a Poor Serum Biomarker of Murine Traumatic Brain Injury After Polytrauma.

Background: Several serum biomarkers have been studied to diagnose incidence and severity of traumatic brain injury (TBI), but a reliable biomarker in TBI has yet to be identified. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker in clinical and preclinical studies, largely in the setting of isolated TBI or concussion. The aim of this study was to evaluate the performance of UCH-L1 as a serum biomarker in the setting of polytrauma and TBI.

Consumptive coagulopathy is associated with organ dysfunction during PICS.

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Although sepsis is characterized by early hypercoagulability and delayed hypocoagulability, coagulopathy during chronic critical illness is not fully understood. The objective of this study was to determine whether sepsis-induced PICS is associated with coagulation abnormalities.

Effects of Early Altitude Exposure on the Open Abdomen After Laparotomy in Trauma.

Introduction: While damage control surgery and resuscitation techniques have revolutionized the care of injured service members who sustain severe traumatic hemorrhage, the physiologic and inflammatory consequences of hemostatic resuscitation and staged abdominal surgery in the face of early aeromedical evacuation (AE) have not been investigated. We hypothesized that post-injury AE with an open abdomen would have significant physiologic and inflammatory consequences compared to AE with a closed abdomen.

Materials And Methods: Evaluation of resuscitation and staged abdominal closure was performed using a murine model of hemorrhagic shock with laparotomy.

Microvesicles generated following traumatic brain injury induce platelet dysfunction via adenosine diphosphate receptor.

Background: Traumatic brain injury (TBI) can result in an acute coagulopathy including platelet dysfunction that can contribute to ongoing intracranial hemorrhage. Previous studies have shown adenosine diphosphate (ADP)-induced platelet aggregation to be reduced after TBI. In addition, circulating microvesicles (MVs) are increased following TBI and have been shown to play a role in post-TBI coagulopathy and platelet function.

Variable saline resuscitation in a murine model of combined traumatic brain injury and haemorrhage.

Background: Resuscitation strategies for combined traumatic brain injury (TBI) with haemorrhage in austere environments are not fully established. Our aim was to establish the effects of various saline concentrations in a murine model of combined TBI and haemorrhage, and identify an effective resuscitative strategy for the far-forward environment.

Methods: Male C57BL/6 mice underwent closed head injury and subjected to controlled haemorrhage to a systolic blood pressure of 25 mmHg via femoral artery cannulation for 60 min.

Amitriptyline Treatment Mitigates Sepsis-Induced Tumor Necrosis Factor Expression and Coagulopathy.

During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis-cecal ligation and puncture (CLP).

Platelet Function Changes in a Time-Dependent Manner Following Traumatic Brain Injury in a Murine Model.

Traumatic brain injury (TBI) results in systemic changes in coagulation and inflammation that contribute to post-traumatic morbidity and mortality. The potential interaction of platelets and pro-inflammatory cytokines in the modulation of coagulation, microthrombosis, and venous thromboembolic events after moderate TBI has not been determined. Using a murine model, we hypothesized that the degree of platelet-induced coagulation varies depending on the platelet aggregation agonist platelet-induced coagulation changes in a time-dependent manner following TBI, and changes in platelet-induced coagulation are mirrored by changes in the levels of circulating pro-inflammatory cytokines.

Impact of tranexamic acid on coagulation and inflammation in murine models of traumatic brain injury and hemorrhage.

Background: Posttraumatic coagulopathy and inflammation can exacerbate secondary cerebral damage after traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown clinically to reduce mortality in hemorrhaging and head-injured trauma patients and has the potential to mitigate secondary brain injury with its reported antifibrinolytic and antiinflammatory properties. We hypothesized that TXA would improve posttraumatic coagulation and inflammation in a murine model of TBI alone and in a combined injury model of TBI and hemorrhage (TBI/H).

ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway.

Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury.

An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn.

Microparticles impact coagulation after traumatic brain injury.

Background: The pathophysiology that drives the subacute hypercoagulable state commonly seen after traumatic brain injury (TBI) is not well understood. Alterations caused by TBI in platelet and microparticle (MP) numbers and function have been suggested as possible causes; however, the contributions of platelets and MPs are currently unknown.

Materials And Methods: A weight-drop technique of TBI using a murine model of moderate head injury was used.

The transcriptome of utricle hair cell regeneration in the avian inner ear.

Sensory hair cell loss is the major cause of hearing and balance disorders. Mammals are incapable of sustained hair cell regeneration, but lower vertebrates can regenerate these mechano-electrical transducers. We present the first comprehensive transcriptome (by mRNA-Seq) of hair cell regeneration in the chick utricle.

A cross-species analysis of microRNAs in the developing avian face.

Higher vertebrates use similar genetic tools to derive very different facial features. This diversity is believed to occur through temporal, spatial and species-specific changes in gene expression within cranial neural crest (NC) cells. These contribute to the facial skeleton and contain species-specific information that drives morphological variation.

An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear.

Sensory hair cells of the inner ear are the mechanoelectric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Nonmammalian vertebrates such as birds can regenerate hair cells after injury.

Downstream targets of GATA3 in the vestibular sensory organs of the inner ear.

Haploinsufficiency for the transcription factor GATA3 leads to hearing loss in humans. It is expressed throughout the auditory sensory epithelium (SE). In the vestibular organs, GATA3 is limited to the striola reversal zone of the utricle.

Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation.

Objective: To determine gene(s) disrupted in a patient with partial frontal lobe epilepsy and cognitive impairment with concomitant de novo balanced chromosomal translocation t(2;13)(q24;q31).

Design: Fluorescence in situ hybridization and array comparative genomic hybridization were used to map the locations of chromosomal translocation breakpoints.

Results: SLC4A10 (OMIM 605556), a sodium bicarbonate transporter gene with high expression in the cerebral cortex and hippocampus, was disrupted by the translocation breakpoint on chromosome 2q24.