Severe Contusion Research Articles

Oxygenation and Respiratory System Compliance Associated With Pulmonary Contusion.

Blunt pulmonary contusions are associated with severe chest injuries and are independently associated with worse outcomes. Previous preclinical studies suggest that contusion progression precipitates poor pulmonary function; however, there are few current clinical data to corroborate this hypothesis. We examined pulmonary dynamics and oxygenation in subjects with pulmonary contusions to evaluate for impaired respiratory function. A chest injury database was reviewed for pulmonary contusions over 5 years at an urban trauma center. This database was expanded to capture mechanical ventilation parameters for the first 7 days on all patients with pulmonary contusion and who were intubated. Daily [Formula: see text]:[Formula: see text], oxygenation indexes (OI), and dynamic compliances were calculated. Pulmonary contusions were stratified by severity. The Fisher exact and chi square tests were performed on categorical variables, and Mann-Whitney U-tests were performed on continuous variables. Significance was assessed at a level of 0.05. 1,176 patients presented with pulmonary contusions, of whom, 301 subjects (25.6%) required intubation and had available invasive mechanical ventilation data. Of these, 144 (47.8%) had mild-moderate pulmonary contusion and 157 (52.2%) had severe pulmonary contusion. Overall injury severity score was high, with a median injury severity score of 29 (interquartile range, 22-38). The median duration of mechanical ventilation for mild-moderate pulmonary contusion was 7 d versus 10 d for severe pulmonary contusion (P = .048). All the subjects displayed moderate hypoxemia, which worsened until day 4-5 after intubation. Severe pulmonary contusion was associated with significantly worse early hypoxia on day 1 and day 2 versus mild-moderate pulmonary contusion. Severe pulmonary contusion also had a higher oxygenation index than mild-moderate pulmonary contusion. This trend persisted after adjustment for other factors, including transfusion and fluid administration. Pulmonary contusions played an important role in the course of subjects who were acutely injured and required mechanical ventilation. Contusions were associated with hypoxemia not fully characterized by [Formula: see text]: [Formula: see text], and severe contusions had durable elevations in the oxygenation index despite confounders.

Blush in Lung Contusions Is Not Rare and Has a High Risk of Mortality in Patients With Blunt Chest Trauma.

BackgroundPatients with blunt chest trauma have a high mortality rate. The assessment of blush in hepatic and splenic trauma is important for determining the need for emergency hemostatic interventions. However, the frequency and importance of blush in lung contusions are unknown. Therefore, this study aimed to evaluate the frequency of blush in patients with lung contusions and elucidate the relationship between blush and the clinical outcomes of patients with blunt chest trauma.Materials and MethodsIn this retrospective observational study, we enrolled patients with an injury severity score of 16 or higher and a chest abbreviated injury scale (AIS) score of 3 or higher who were admitted to the emergency department of Hokkaido University Hospital from January 1, 2003, to December 31, 2016. Blush was defined as active extravasation of an intravascular contrast agent recognized on contrast-enhanced computed tomography. The date of trauma, trauma severity, treatments, and outcomes were obtained from the patients’ electronic medical records.ResultsDuring the study period, 83 patients had severe lung contusions and 13 had blush. In-hospital mortality of patients with blush was significantly higher than that of patients without blush (53 vs. 10%, P < 0.001). Patients with blush required thoracic drainage more frequently (100 vs. 71%, P < 0.001) and support through mechanical ventilation more often (100 vs. 64%, P < 0.001) and for a longer duration (median duration, 0 vs. 25 days, P = 0.001) than patients without blush.ConclusionsOur study revealed that blush in lung contusions was not rare and was associated with a high risk of mortality in patients with severe blunt chest trauma. Clinicians should not hesitate to intervene if blush is detected in a lung contusion of a patient with blunt chest trauma.

The Validity of Quantifying Pulmonary Contusion Extent by Lung Ultrasound Score for Predicting ARDS in Blunt Thoracic Trauma

Background Thoracic trauma comprises 20–25% of all traumas worldwide and constitutes the third most common cause of death after abdominal injury and head trauma in polytrauma patients. Pulmonary contusion (PC) is a common injury seen after blunt trauma that is associated with significant morbidity and mortality. The aim of this prospective study was to determine the value of PC extent measurements using lung ultrasound in predicting high risk patients for ARDS development. Methods In one year, 50 polytrauma patients with blunt chest trauma were admitted to the ICU at Damanhur Institute. Lung contusion extent was evaluated using a lung US score (LUS) and was compared to the CT contusion score. The ability of the LUS to predict ARDS was tested. The diagnostic accuracy of LUS was compared with chest radiography for lung contusion and pneumothorax with thoracic CT scan as a reference. Patients were restratified by LUS into two groups: severe and nonsevere contusion group. The two groups' data were compared with respect to difference in mortality and injury characteristics. Results Lung contusion assessed by LUS score was well correlated to thoracic CT scan measurements (r = 0.78). A LUS of 4 was defined as a cut-off value for predicting ARDS development within 72 hours of trauma with sensitivity and specificity (91.67% and 84.21%), respectively. Patients with severe lung contusions had a lower hypoxic index on admission, more ventilator days, a higher risk of ARDS development, more fractured ribs; higher rate of hemothorax and a higher ISS score than patients with nonsevere lung contusions. Conclusion LUS on admission can quantify lung contusion extent and the high risk of developing ARDS after blunt thoracic trauma.

Neuroanatomical Remodeling of Colonic Interstitial Cells of Cajal after Spinal Cord Injury

After spinal cord injury (SCI), individuals often experience gastrointestinal comorbidities including neurogenic bowel, a condition where colonic dysmotility causes chronic constipation, difficulty with evacuation and overflow incontinence. Located intrinsic to the gastrointestinal (GI) tract, the anatomy of the enteric nervous system (ENS) is not directly damaged at the time of the initial spinal trauma, thereby serving as a potential pharmacologic target for neurogenic bowel. Enteric neuromuscular control of colonic slow‐wave propagation is a balance of excitatory and inhibitory inputs to Interstitial Cells of Cajal (ICC), pacemaker cells that are interposed between enteric neurons and smooth muscle cells. Reduction of colonic ICCs accompany colonic dysmotility in other disease states and our lab has previously shown a reduction in cholinergic and nitrergic enteric neurons following experimental SCI. Of the ICC subtypes, those of the myenteric plexus are strongly associated with driving colonic motility. We hypothesized that after SCI, the distal colon myenteric plexus ICCs will present with decreased cell bodies and projection length in both sexes, contributing to neurogenic bowel.This study aims to expand current understanding of neurogenic bowel neuroanatomy in acute 3‐day and chronic 3‐week SCI rats. Experimentally, male and female rats receive a surgical control or severe T3 contusion SCI (n = 19 M, 22 F). Three days or three weeks post‐operatively, the distal colon smooth muscle tissue is harvested and dissected for immunohistochemical (IHC) and electrophysiological analysis. C‐Kit antibody is then used to fluorescently label the ICCs, upon which we quantified myenteric plexus cell bodies and projection length. Unexpectedly, the myenteric plexus presented with a significant increase in cell count (p = &lt;0.01) and projection length (p = &lt;0.01) following SCI compared to control animals in both sexes. Additionally, a significant interaction effect was observed between animal time point and surgical group for cell count (p = &lt;0.01) and a significant interaction between sex and surgical group for projection length (p = &lt;0.03). The current data illustrates sex‐related differences in remodeling of the colonic neuromuscular interface after SCI, reinforcing the importance of sex‐specific treatment for neurogenic bowel to improve clinical outcomes. The enduring plasticity of the ICC in our chronic animal model demonstrates the importance of continual medication adjustments among the SCI population. Myenteric ICC network upregulation may reflect a compensatory response to diminished cholinergic enteric neuronal input, therefore our future studies will investigate cholinergic receptor neurophysiology after SCI.

The method of quantitative assessment of posttraumatic spinal cord injury volume and structure in animal models using magnetic resonance tomography

Introduction. Spinal cord injury is a debilitating traumatic event in central nervous system resulting in tissue destruction and severe neurological deficit development. Preclinical assessment of quantitative lesion area parameters (e. g. structure and volume) is critical for subsequent evaluation of neuroprotective and / or neuroregenerative therapy efficiency. Current methods for parameter calculation require manual limitation of the interested area (region of interest, RoI). This process is tedious and often not precise enough.Study objective is to develop and implement software for automated assessment of volume and structure of posttraumatic spinal cord lesion using extra-high-field MRI 7.0 Tesla and to compare methods preciseness with the current manual techniques.Study design. Ten rat models of acute severe spinal cord contusion injury were used including female Sprague–Dawley animals weighting 250–350 gr. MRI imaging was performed in 1 day postoperative and then 4 times with interval (1 week). Study was prospective open-label uncontrolled comparative.Materials and methods. Standard spinal cord contusion injury model was used. Anesthetized animals underwent laminectomy at level Th9–Th10 vertebrae followed by “weight drop” injury technique application: 10 g weight with 2 mm pin diameter dropped from 25 mm height. Software was developed using Microsoft Visual Studio 2017 environment and programming language C#. Statistical analysis was performed using IBM SPSS Statistics 21.0 software.Results. We developed and patented specialized software Spinal cavity Searcher realizing the algorithm of T2‑weighted images (T2‑WI) analysis based on image bynarization and Freeman chain code. This algorithm supports calculation of spinal cord posttraumatic lesion parameters in a half-automatic manner. Results of this algorithm application were comparable to results of manual calculation: no statistical difference were observed between two values.Conclusion. Current method of spinal cord injury volume and structure quantitative assessment simplifies the calculation procedure due to automatization of RoI limitation comparing to manual technique. The level of preciseness is comparable in both methods.Clinical relevance. The developed algorithm optimizes the process of non-invasive control of the performed treatment efficiency according to 7.0 Tesla MRI data.

Evaluation of the Cardiometabolic Disorders after Spinal Cord Injury in Mice.

Simple SummaryThe present study demonstrates severity-dependent effects of a thoracic T8 injury on cardiometabolic dysfunctions in adult mice. While these chronic cardiometabolic issues can be multifactorial, the data indicate that systemic inflammatory response is likely to be involved. These findings are supportive of the role of systemic inflammation following SCI being critical in identifying therapeutic targets and predicting long-term outcomes.Changes in cardiometabolic functions contribute to increased morbidity and mortality after chronic spinal cord injury. Despite many advancements in discovering SCI-induced pathologies, the cardiometabolic risks and divergences in severity-related responses have yet to be elucidated. Here, we examined the effects of SCI severity on functional recovery and cardiometabolic functions following moderate (50 kdyn) and severe (75 kdyn) contusions in the thoracic-8 (T8) vertebrae in mice using imaging, morphometric, and molecular analyses. Both severities reduced hindlimbs motor functions, body weight (g), and total body fat (%) at all-time points up to 20 weeks post-injury (PI), while only severe SCI reduced the total body lean (%). Severe SCI increased liver echogenicity starting from 12 weeks PI, with an increase in liver fibrosis in both moderate and severe SCI. Severe SCI mice showed a significant reduction in left ventricular internal diameters and LV volume at 20 weeks PI, associated with increased LV ejection fraction as well as cardiac fibrosis. These cardiometabolic dysfunctions were accompanied by changes in the inflammation profile, varying with the severity of the injury, but not in the lipid profile nor cardiac or hepatic tyrosine hydroxylase innervation changes, suggesting that systemic inflammation may be involved in these SCI-induced health complications.

Factors related to clinical outcomes in blunt thoracic injuries.

This study aims to reduce mortality and morbidity by analyzing the factors associated with blunt chest trauma. In this study, 1020 patients with blunt thoracic trauma were analyzed retrospectively. Major surgeries, complications, admission to intensive care unit, intubation, mortality, prolonged hospital stay were considered poor clinical outcomes. Independent variables were compared with clinical outcomes and analyzed. The mean age was 52.7 ± 19.1. Complications (p = 0.028) and mortality (p < 0.001) were higher in patients aged 65years and older than those aged 65years and younger. Severe chest wall injuries, hemopneumothorax, and pulmonary contusions were associated with poor clinical outcomes (OR = 2474, p = 0.001, OR = 2229, p < 0.001 and OR = 2229, p < 0.001, respectively). The variable most related to poor clinical outcomes was New Injury Severity Score (p < 0.001, OR = 8.37). The most associated factor with poor clinical outcomes was injury severity. Prompt treatment of blunt chest trauma with timely chest tube thoracostomy or surgical treatment when necessary, optimal pain control, and chest physiotherapy will reduce mortality.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Inositol Polyphosphate-5-Phosphatase K (Inpp5k) Enhances Sprouting of Corticospinal Tract Axons after CNS Trauma.

Failure of CNS neurons to mount a significant growth response after trauma contributes to chronic functional deficits after spinal cord injury. Activator and repressor screening of embryonic cortical neurons and retinal ganglion cells in vitro and transcriptional profiling of developing CNS neurons harvested in vivo have identified several candidates that stimulate robust axon growth in vitro and in vivo Building on these studies, we sought to identify novel axon growth activators induced in the complex adult CNS environment in vivo We transcriptionally profiled intact sprouting adult corticospinal neurons (CSNs) after contralateral pyramidotomy (PyX) in nogo receptor-1 knock-out mice and found that intact CSNs were enriched in genes in the 3-phosphoinositide degradation pathway, including six 5-phosphatases. We explored whether inositol polyphosphate-5-phosphatase K (Inpp5k) could enhance corticospinal tract (CST) axon growth in preclinical models of acute and chronic CNS trauma. Overexpression of Inpp5k in intact adult CSNs in male and female mice enhanced the sprouting of intact CST terminals after PyX and cortical stroke and sprouting of CST axons after acute and chronic severe thoracic spinal contusion. We show that Inpp5k stimulates axon growth in part by elevating the density of active cofilin in labile growth cones, thus stimulating actin polymerization and enhancing microtubule protrusion into distal filopodia. We identify Inpp5k as a novel CST growth activator capable of driving compensatory axon growth in multiple complex CNS injury environments and underscores the veracity of using in vivo transcriptional screening to identify the next generation of cell-autonomous factors capable of repairing the damaged CNS.SIGNIFICANCE STATEMENT Neurologic recovery is limited after spinal cord injury as CNS neurons are incapable of self-repair post-trauma. In vitro screening strategies exploit the intrinsically high growth capacity of embryonic CNS neurons to identify novel axon growth activators. While promising candidates have been shown to stimulate axon growth in vivo, concomitant functional recovery remains incomplete. We identified Inpp5k as a novel axon growth activator using transcriptional profiling of intact adult corticospinal tract (CST) neurons that had initiated a growth response after pyramidotomy in plasticity sensitized nogo receptor-1-null mice. Here, we show that Inpp5k overexpression can stimulate CST axon growth after pyramidotomy, stroke, and acute and chronic contusion injuries. These data support in vivo screening approaches to identify novel axon growth activators.

Systemic Administration of Allogeneic Cord Blood Mononuclear Cells in Adults with Severe Acute Contusion Spinal Cord Injury: Phase 1/2a Pilot Clinical Study–Safety and Primary Efficacy Evaluation

Phase 1 of the SUBSCI I/IIa (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury) study focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit. The primary end point was safety. The secondary end point was the restoration of motor and sensory function in lower limbs within a 1-year period. Ten patients with acute contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit were enrolled into phase 1. Patients were treated with 4 infusions of group-matched and rhesus-matched cord blood samples after primary surgery within 3 days after SCI. All patients were followed up for 12 months after SCI. Safety was assessed using adverse events classification depending on severity and relation to cell therapy. Primary efficacy was assessed using dynamics of deficit (ASIA scale). The overall number of adverse events reached 419 in 10 patients. Only 2 were estimated as possibly related to cell therapy, and the remaining 417 were definitely unrelated. Both adverse events were mild and clinically insignificant. No signs of immunization were found in participants. Analysis of clinical outcomes also showed that cell therapy promotes significant functional restoration of motor function. The data obtained suggest that systemic administration of allogeneic, non-human leukocyte antigen-matched human umbilical cord blood is safe and shows primary efficacy in adults with severe acute contusion SCI and ASIA level A/B deficit.

Застосування препарату Гліатилін при консервативній фармакотерапії тяжкої черепно-мозкової травми з контузійним ураженням речовини головного мозку

Наведені дані дослідження ефективності препарату Гліатилін (холіну альфосцерат) у терапії гострого періоду черепно-­мозкової травми (ЧМТ), забою головного мозку тяжкого ступеня з порушенням свідомості у випадку, коли оперативне втручання не показано, але є верифіковані контузійні вогнища з порушенням свідомості. У дослідження були включені 40 пацієнтів (28 чоловіків і 12 жінок) віком від 21 до 63 років (середній вік — 42 роки) із ЧМТ тяжкого ступеня. Пацієнти були розділені на 2 групи по 20 осіб (по 14 чоловіків та 6 жінок) за призначеною терапією. I група отримувала стандартизовану метаболічну, протинабрякову, антибіотикотерапію та ноотропну терапію. II група — таку ж терапію, доповнену Гліатиліном у дозі 1000 мг/добу внутрішньовенно краплинно. На тлі проведеної фармакотерапії в динаміці відстежувалася її ефективність протягом усього курсу (14 діб) за шкалою коми Глазго, за даними епідурального сенсора внутрішньочерепного тиску та за даними спіральної комп’ютерної томограми головного мозку.

Impact caused a severe contusion to the spinal cord and issues of concern forensic of degree of injury to health

Impact caused a severe contusion to the spinal cord and issues of concern forensic of degree of injury to health

Selective Myostatin Inhibition Spares Sublesional Muscle Mass and Myopenia-Related Dysfunction after Severe Spinal Cord Contusion in Mice.

Clinically relevant myopenia accompanies spinal cord injury (SCI), and compromises function, metabolism, body composition, and health. Myostatin, a transforming growth factor (TGF)β family member, is a key negative regulator of skeletal muscle mass. We investigated inhibition of myostatin signaling using systemic delivery of a highly selective monoclonal antibody - muSRK-015P (40 mg/kg) - that blocks release of active growth factor from the latent form of myostatin. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kdyn) at T9 and were then immediately and 1 week later administered test articles: muSRK-015P (40 mg/kg) or control (vehicle or IgG). A sham control group (laminectomy only) was included. At euthanasia, (2 weeks post-SCI) muSRK-015P preserved whole body lean mass and sublesional gastrocnemius and soleus mass. muSRK-015P-treated mice with SCI also had significantly attenuated myofiber atrophy, lipid infiltration, and loss of slow-oxidative phenotype in soleus muscle. These outcomes were accompanied by significantly improved sublesional motor function and muscle force production at 1 and 2 weeks post-SCI. At 2 weeks post-SCI, lean mass was significantly decreased in SCI-IgG mice, but was not different in SCI-muSRK-015P mice than in sham controls. Total energy expenditure (kCal/day) at 2 weeks post-SCI was lower in SCI-immunoglobulin (Ig)G mice, but not different in SCI-muSRK-015P mice than in sham controls. We conclude that in a randomized, blinded, and controlled study in mice, myostatin inhibition using muSRK-015P had broad effects on physical, metabolic, and functional outcomes when compared with IgG control treated SCI animals. These findings may identify a useful, targeted therapeutic strategy for treating post-SCI myopenia and related sequelae in humans.

The Association Between Pulmonary Contusion Severity and Respiratory Failure.

Pulmonary contusions (PCs) have historically been viewed as a serious complicating factor in thoracic injury. Recently, there has been conflicting evidence regarding the influence of PCs on outcomes; however, many studies do not stratify contusions by severity and may miss clinical associations. We sought to identify if contusion severity is associated with worse outcomes. A previously published chest wall injury database at an urban Level I trauma center was retrospectively reviewed. All severely injured subjects (defined as Injury Severity Score [ISS] ≥ 15) with moderate to severe thoracic injury (defined as a chest wall Abbreviated Injury Scale [AIS] ≥ 3) who required mechanical ventilation for > 24 h were stratified by contusion severity. Moderate to severe contusions were defined as AIS contusion ≥ 3 and Blunt Pulmonary Contusion 18 (BPC18) score ≥ 3. Over 5 y, 3,836 patients presented with chest wall injuries, of which 1,176 (30.6%) had concomitant contusions. When screened for inclusion criteria, 339 subjects with contusions and 211 subjects without contusions (no-PC) were identified. Of these, 234 had moderate to severe contusions defined by AIS contusion ≥ 3 (PC-A) and 230 had moderate to severe contusions by BPC18 ≥ 3 (PC-B). Compared to no-PC, both PC-A and PC-B groups had significantly lower mortality (17.9% and 17.4%, respectively, vs 28.9%); however, PC-A and PC-B groups had longer durations of mechanical ventilation (6 and 7 d, respectively, vs 5 d), longer ICU length of stay (10 and 10 vs 8 d), and longer overall hospital length of stay (15 and 15 vs 13 d). In severely injured polytrauma patients, PCs are seen with more severe chest injuries. Furthermore, moderate to severe contusions are associated with longer durations of mechanical ventilation, ICU length of stay, and hospital length of stay. Despite practice pattern changes, contusions appear to contribute significantly to the clinical course of the blunt chest wall injured patients.

Morphological changes in the sciatic nerve in experimental modeling of contusion injury of the spinal cord in rats

Objective. To analyze morphological and morphometric changes in the sciatic nerve of rats after the spinal cord injury.Material and Methods. The Т9 moderately severe contusion injury of the spinal cord was simulated in 12 Wistar female rats. Functions of the pelvic limbs were assessed according to the standardized BBB scale. The animals were withdrawn from the experiment after nine and 13 weeks. Epoxy semi-thin (1 µm) sections were used to study sciatic nerve at the light-optical level.Results. Significant recovery of pelvic limb functions was observed within four weeks after surgery, the plateau was achieved by Week 5 (9.5 ± 0.28 points according to the BBB scale), the deterioration in the motor activity was observed by Week 9 (8.67 ± 0.33), its recovery was achieved by Week 13 of the experiment (9.5 ± 0.87). After 9 and 13 weeks, reactive-destructive changes were detected in the sciatic nerve in 9 % and 8 % of nerve conductors, an increase in the number density of myelin fibers by 28 % and 27 % (p &lt; 0.05) and myelin-free fibers by 20 % and 49 % (p &lt; 0.05), and a decrease in axon diameters by 8 % and 10 % (p &lt; 0.05), respectively.Conclusions. The morphological and morphometric changes in the sciatic nerve revealed after the spinal cord injury in the form of destruction of a part of the fibers, axonal atrophy and a decrease in the proportion of large fibers negatively affect its conductive properties. The leveling of peripheral nerve damage, possibly, will accelerate the regression of the motor deficit caused by the spinal cord injury; therefore, it is necessary to develop a set of preventive measures aimed at preventing the reorganization of the peripheral nerve tissue.

Comparative analysis of functional assessment for contusion and transection models of spinal cord injury.

Descriptive secondary analysis of two spinal cord injury (SCI) animal models. To compare the somatosensory evoked potential (SSEP) and motor behavioral (BBB) assessments of the two most used rodent SCI models (contusion and transection), to elucidate their functional similarity and differences over the acute phase of 3 weeks. Neuro-electrophysiology SSEP and motor behavioral BBB assessments are used to provide a comparative analysis of the functional changes among various severities of contusion and transection SCI. Adult male and female rats randomly grouped (n = 5) as following: mild (6.25 mm), moderate (12.5 mm), severe (25 mm), and very severe (50 mm) contusion as well as right T10 hemi-transection (RxI), left T8 and right T10 double hemi-transection (DxI), and T8 complete transection (CxI) injuries, plus the control group (laminectomy with no injury). Animal weight, body temperature, anesthesia, surgical procedures, electrophysiological SSEP monitoring, locomotion BBB scoring, and statistical analysis were identical among all animal groups. Statistical analysis of the SSEP and BBB data from both contusion and transection injury models indicate significant differences (P < 0.05). The results also show remarkable similarity for the severe and very severe contusion injuries to the complete transection, the moderate contusion injury to the double hemi-transection, and the mild contusion injury to the T10 hemi-transection injury. Although contusion and transection spinal cord injuries have two completely different pathophysiologies, their injury progress during acute phase follow a similar trend.

Bone loss after severe spinal cord injury coincides with reduced bone formation and precedes bone blood flow deficits.

Diminished bone perfusion develops in response to disuse and has been proposed as a mechanism underlying bone loss. Bone blood flow (BF) has not been investigated within the unique context of severe contusion spinal cord injury (SCI), a condition that produces neurogenic bone loss that is precipitated by disuse and other physiological consequences of central nervous system injury. Herein, 4-mo-old male Sprague-Dawley rats received T9 laminectomy (SHAM) or laminectomy with severe contusion SCI (n = 20/group). Time course assessments of hindlimb bone microstructure and bone perfusion were performed in vivo at 1- and 2-wk postsurgery via microcomputed tomography (microCT) and intracardiac microsphere infusion, respectively, and bone turnover indices were determined via histomorphometry. Both groups exhibited cancellous bone loss beginning in the initial postsurgical week, with cancellous and cortical bone deficits progressing only in SCI thereafter. Trabecular bone deterioration coincided with uncoupled bone turnover after SCI, as indicated by signs of ongoing osteoclast-mediated bone resorption and a near-complete absence of osteoblasts and cancellous bone formation. Bone BF was not different between groups at 1 wk, when both groups displayed bone loss. In comparison, femur and tibia perfusion was 30%-40% lower in SCI versus SHAM at 2 wk, with the most pronounced regional BF deficits occurring at the distal femur. Significant associations existed between distal femur BF and cancellous and cortical bone loss indices. Our data provide the first direct evidence indicating that bone BF deficits develop in response to SCI and temporally coincide with suppressed bone formation and with cancellous and cortical bone deterioration.NEW & NOTEWORTHY We provide the first direct evidence indicating femur and tibia blood flow (BF) deficits exist in conscious (awake) rats after severe contusion spinal cord injury (SCI), with the distal femur displaying the largest BF deficits. Reduced bone perfusion temporally coincided with unopposed bone resorption, as indicated by ongoing osteoclast-mediated bone resorption and a near absence of surface-level bone formation indices, which resulted in severe cancellous and cortical microstructural deterioration after SCI.

PD27-03 EARLY DETRUSOR CHEMODENERVATION AFTER SPINAL CORD INJURY CAN REDUCE BLADDER HYPERTROPHY AND FIBROSIS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-03 EARLY DETRUSOR CHEMODENERVATION AFTER SPINAL CORD INJURY CAN REDUCE BLADDER HYPERTROPHY AND FIBROSIS Zin Khiang, Juliana Bushnell, Jeffrey Hyde, and Claire Yang Zin KhiangZin Khiang More articles by this author , Juliana BushnellJuliana Bushnell More articles by this author , Jeffrey HydeJeffrey Hyde More articles by this author , and Claire YangClaire Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Following spinal cord injury (SCI), pathological reflexes develop, altering bladder and sphincter function, and resulting in detrusor changes within weeks after injury. Detrusor chemodenervation is known to ablate the pathological reflexes, but its effects on the development of detrusor changes is unknown. In a rodent model of SCI, we examine the effect of early detrusor chemodenervation. METHODS: Adult female Sprague Dawley rats (250–300g) were given a severe contusion SCI with 200-kDyne force with zero dwell time using an Infinite Horizon device following laminectomy, at spinal level T9 (N=8). A group of control rats did not undergo spinal injury (N=3) but underwent laminectomy only. The SCI rats immediately underwent laparotomy, and either saline (N=4) or botulinum toxin A (BoNT-A) 10U (N=4) was injected into the detrusor in 8 equal aliquots of 3 microliters per injection. The animals were sacrificed at 8 weeks post injury (wpi), and the bladders harvested and weighed. Tissue was stained using hematoxylin and eosin and Masson’s trichrome. RESULTS: SCI without bladder chemodenervation (SCI-saline injected) resulted in significantly heavier bladders compared to the bladders of control (spinal-intact) animals (241±25 mg vs. 137±30 mg; p<0.01). BoNT-A injected bladders of SCI rats (SCI-BoNT-A) were significantly lighter compared to saline injected bladders of SCI rats (183±42 mg vs. 241±25 mg; p<0.05). SCI-saline rats had thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from control animals (339±89 mm vs. 193±48 mm; p<0.0002). Bladder wall thickness in the SCI-BoNT-A rats was significantly less compared to SCI-saline rats (202±55 mm vs. 339±89 mm; p<0.0001) (Figure). CONCLUSIONS: Chemodenervation immediately following SCI significantly mitigates the development of pathologic detrusor histology by reducing the development of fibrosis and hypertrophy. Source of Funding: William E. Bradley Family Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e444-e444 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zin Khiang More articles by this author Juliana Bushnell More articles by this author Jeffrey Hyde More articles by this author Claire Yang More articles by this author Expand All Advertisement Loading ...

Chest Wall Reconstruction for the Treatment of Lung Herniation and Respiratory Failure 1 Month after Emergency Thoracotomy in a Patient with Traumatic Flail Chest

We report a case of delayed chest wall reconstruction after thoracotomy. A 53-year-old female, a victim of a motor vehicle accident, presented with bilateral multiple rib fractures with flail motion and multiple extrathoracic injuries. Whole-body computed tomography revealed multiple fractures of the bilateral ribs, clavicle, and scapula, and bilateral hemopneumothorax with severe lung contusions. Active hemorrhage was also found in the anterior pelvis, which was treated by angioembolization. The patient was transferred to the surgical intensive care unit for follow-up. We planned to perform surgical stabilization of rib fractures (SSRF) because her lung condition did not seem favorable for general anesthesia. Within a few hours, however, massive hemorrhage (presumably due to coagulopathy) drained through the thoracic drainage catheter. We performed an exploratory thoracotomy in the operating room. We initially planned to perform exploratory thoracotomy and “on the way out” SSRF. In the operating room, the hemorrhage was controlled; however, her condition deteriorated and SSRF could not be completed. SSRF was completed after about a month owing to other medical conditions, and the patient was weaned successfully.

Valproic Acid Ameliorates Locomotor Function in the Rat Model of Contusion via Alteration of Mst1, Bcl-2, and Nrf2 Gene Expression.

Background:In animal models of inflammatory diseases, Mst1 facilitates the programmed cell death as a novel pro-apoptotic kinase. This research aimed to determine the expression level of Mst1 gene in a rat model of SCI treated with VPA. Methods:Severe rat model contusion was used for evaluation of the neuroprotective effect of valproic acid. The BBB test, was performed to determine locomotor functions. H&E staining and TUNEL assay were performed to detect cavity formation and apoptosis, respectively. The mRNA levels of the genes Mst1, Nrf2, and Bcl-2 were evaluated, using quantitative RT-PCR. Results:The results revealed that Mst1 gene expression and TUNEL-positive cells in the VPA-treated group were significantly reduced as compared to the untreated group (p ≤ 0.05). Conclusion:Our findings indicate that VPA has therapeutic potential and can be a candidate for the treatment of neurodegenerative disorders and traumatic injury as a promising drug.