Correction: Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model.
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ABSTRACT:
SUBMITTER: Hsieh TH
PROVIDER: S-EPMC5524354 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:ObjectiveTraumatic brain injury (TBI) is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.ApproachThe acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.ResultsGradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.ConclusionsWe conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.
| S-EPMC5446124 | biostudies-literature
Project description:Cardiac dysfunction (CD) importantly contributes to mortality in trauma patients, who survive their initial injuries following successful hemostatic resuscitation. This poor outcome has been correlated with elevated biomarkers of myocardial injury, but the pathophysiology triggering this CD remains unknown. We investigated the pathophysiology of acute CD after trauma using a mouse model of trauma hemorrhage shock (THS)-induced CD with echocardiographic guidance of fluid resuscitation, to assess the THS impact on myocardial integrity and function. Mice were subjected to trauma (soft tissue and bone fracture) and different degrees of hemorrhage severity (pressure controlled ~MABP < 35 mmHg or <65 mmHg) for 1 h, to characterize the acute impact on cardiac function. In a second study, mice were subjected to trauma and hemorrhage (MABP < 35 mmHg) for 1 h, then underwent two echocardiographic-guided resuscitations to baseline stroke volume at 60 and 120 min, and were monitored up to 180 min to study the longer impact of THS following resuscitation. Naïve and sham animals were used as controls. At 60 min post-THS injury, animals showed a lower cardiac output (CO) and stroke volume (SV) and an early rise of heart fatty acid-binding protein (H-FABP = 167 ± 38 ng/ml; 90% increase from shams, 3.54 ± 3.06 ng/ml), when subjected to severe hemorrhage and injury. Despite resuscitation, these animals maintained lower CO (6 ml/min vs. 23 ml/min), lower SV (10 μl vs. 46 μl; both ~75% decreased), and higher H-FABP (levels (340 ± 115 ng/ml vs. 10.3 ± 0.2 ng/ml; all THS vs. shams, P < 0.001) at 180 min post-THS injury. Histopathological and flow-cytometry analysis of the heart confirmed an influx of circulatory leukocytes, compared to non-injured hearts. Myocardial injury was supported by an increase of troponin I and h-FABP and the widespread ultrastructural disorganization of the morphology of sarcomeres and mitochondria. DNA fragmentation and chromatin condensation driven by leakage of apoptosis-inducing factor (AIF) may suggest a mitochondria-driven progressive cell death. THS modeling in the mouse results in cardiomyocyte damage and reduced myocardial function, which mimics the cardiac dysfunction seen in trauma patients. This CD model may, therefore, provide further understanding to the mechanisms underlying CD and act as a tool for developing cardioprotective therapeutics to improve survival after injury.
| S-EPMC6908477 | biostudies-literature
Project description:Hybrid PET and MR scanners have become a reality in recent years, with the benefits of reduced radiation exposure, reduction of imaging time, and potential advantages in quantification. Appropriate attenuation correction remains a challenge. Biases in PET activity measurements were demonstrated using the current MR-based attenuation-correction technique. We aimed to investigate the impact of using a standard MR-based attenuation correction technique on the clinical and research utility of a PET/MR hybrid scanner for amyloid imaging.Florbetapir scans were obtained for 40 participants on a hybrid scanner with simultaneous MR acquisition. PET images were reconstructed using both MR- and CT-derived attenuation maps. Quantitative analysis was performed for both datasets to assess the impact of MR-based attenuation correction to absolute PET activity measurements as well as target-to-reference ratio (SUVR). Clinical assessment was also performed by a nuclear medicine physician to determine amyloid status based on the criteria in the Food and Drug Administration prescribing information for florbetapir.MR-based attenuation correction led to underestimation of PET activity for most parts of the brain, with a small overestimation for deep brain regions. There was also an overestimation of SUVRs with cerebellar reference. SUVR measurements obtained from the 2 attenuation-correction methods were strongly correlated. Clinical assessment of amyloid status resulted in identical classification as positive or negative regardless of the attenuation-correction methods.MR-based attenuation correction causes biases in quantitative measurements. The biases may be accounted for by a linear model, although the spatial variation cannot be easily modeled. The quantitative differences, however, did not affect clinical assessment as positive or negative.
| S-EPMC4891225 | biostudies-literature
Project description:Central nervous system injury causes a marked increase in the expression of cell cycle-related proteins. In this study, we show that cell cycle activation (CCA) is detected in mature neurons at 24 hours after rat lateral fluid percussion (LFP)-induced traumatic brain injury (TBI), as reflected by increased expression of cyclin G1, phosphorylated retinoblastoma (phospho-Rb), E2F1 and proliferating cell nuclear antigen (PCNA). These changes were associated with progressive cortical, hippocampal, and thalamic neuronal loss and microglial and astrocyte activation. Notably, we detected 5-bromo-2'-deoxyuridine (BrdU)-positive neurons, microglia, and astrocytes at 7 days, but not at 24 hours, suggesting that cell cycle reaches the S phase in these cell types at the latter time point. A delayed systemic post-LFP administration at 3 hours of CR8--a potent second-generation cyclin-dependent kinase (CDK) inhibitor--reduced CCA; cortical, hippocampal, and thalamic neuronal loss; and cortical microglial and astrocyte activation. Furthermore, CR8 treatment attenuated sensorimotor and cognitive deficits, alleviated depressive-like symptoms, and decreased lesion volume. These findings underscore the contribution of CCA to progressive neurodegeneration and chronic neuroinflammation following TBI, and demonstrate the neuroprotective potential of cell cycle inhibition in a clinically relevant experimental TBI model.
| S-EPMC3948132 | biostudies-other
Project description:Age/gender may likely influence the course of septic complications after trauma. We aimed to characterize the influence of age/gender on the response of circulating cytokines, cells and organ function in post-traumatic sepsis. We additionally tested whether post-traumatic responses alone can accurately predict outcomes in subsequent post-traumatic sepsis. A mouse 2-hit model of trauma/hemorrhage (TH, 1(st) hit) and cecal ligation and puncture (CLP, 2(nd) hit) was employed. 3, 15 and 20 month (m) old female (?) and male (?) CD-1 mice underwent sublethal TH followed by CLP 2 days later. Blood was sampled daily until day 6 post-TH and survival was followed for 16 days. To compare general response patterns among groups, we calculated two scores: the inflammatory response (including KC, MIP-1?, TNF?, MCP-1, IFN?, IL-1?,-5,-6,-10) and the organ dysfunction score (Urea, ALT, AST and LDH). Moreover, mice were retrospectively divided into survivors (SUR) and dying (DIE) based on post-CLP outcome. In general, females survived better than males and their survival did not correspond to any specific estrus cycle phase. Pre-CLP phase: the post-TH inflammatory score was weakest in 3 m? but there were no changes among remaining groups (similar lack of differences in the organ dysfunction score). TH induced a 40% increase of IFN?, MIP-1? and IL-5 in 15 m? SUR (vs. DIE) but predictive accuracy for post-CLP outcomes was moderate. Post-CLP phase: while stable in males, inflammatory response score in 15 m and 20 m females decreased with age at day 1 and 2 post-CLP. SUR vs. DIE differences in inflammatory and organ dysfunction score were evident but their magnitude was comparable across age/gender. Nearly identical activation of the humoral inflammatory and organ function compartments, both across groups and according to sepsis severity, suggests that they are not directly responsible for the age/gender-dependent disparity in TH-CLP survival in the studied young-to-mature population.
| S-EPMC3520804 | biostudies-literature
Project description:Early declines in gonadotropin production, despite elevated serum estradiol, among some individuals with severe traumatic brain injury (TBI) suggests amplified systemic aromatization occurs post-injury. Our previous work identifies estradiol (E2) as a potent mortality marker. Androstenedione (A), a metabolic precursor to E2, estrone (E1), and testosterone (T), is a steroid hormone substrate for aromatization that has not been explored previously as a biomarker in TBI. Here, we evaluated serum A, E1, T, and E2 values for 82 subjects with severe TBI. Daily hormone values were calculated, and E2:A and E1:T ratios were generated and then averaged for days 0-3 post-injury. After data inspection, mean E2:A values were categorized as above (high aromatization) and below (low aromatization) the 50th percentile for 30-day mortality assessment using Kaplan-Meier survival analysis and a multivariable Cox proportional hazard model adjusting for age, and Glasgow Coma Scale (GCS) to predict 30-day mortality status. Daily serum T, E1, and E2 were graphed by E2:A category. Serum E1 and E2 significantly differed over time (p?<?0.05); the high aromatization group had elevated levels and a significantly lower probability of survival within the first 30 days (p?=?0.0274). Multivariable Cox regression showed a significant E2:A*GCS interaction (p?=?0.0129), wherein GCS predicted mortality only among those in the low aromatization group. E2:A may be a useful mortality biomarker representing enhanced aromatization after TBI. E2:A ratios may represent non-neurological organ dysfunction after TBI and may be useful in defining injury subgroups in which GCS has variable capacity to serve as an accurate early prognostic marker.
| S-EPMC6354608 | biostudies-literature
Project description:In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14?days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. METHODS:Rats pups received erythropoietin or vehicle at 1, 24, and 48?h and 7?days after injury or sham surgery followed by histology at 35?days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. RESULTS:Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. CONCLUSIONS:Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury.
| S-EPMC5878733 | biostudies-literature
Project description:Background/objectiveMultimodality neurologic monitoring (MMM) is an emerging technique for management of traumatic brain injury (TBI). An increasing array of MMM-derived biomarkers now exist that are associated with injury severity and functional outcomes after TBI. A standardized MMM reporting process has not been well described, and a paucity of evidence exists relating MMM reporting in TBI management with functional outcomes or adverse events.MethodsProspective implementation of standardized MMM reporting at a single pediatric intensive care unit (PICU) is described that included monitoring of intracranial pressure (ICP), cerebral oxygenation and electroencephalography (EEG). The incidence of clinical decisions made using MMM reporting is described, including timing of neuroimaging, ICP monitoring discontinuation, use of paralytic, hyperosmolar and pentobarbital therapies, neurosurgical interventions, ventilator and CPP adjustments and neurologic prognostication discussions. Retrospective analysis was performed on the association of MMM reporting with initial Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, duration of total hospitalization and PICU hospitalization, duration of mechanical ventilation and invasive ICP monitoring, inpatient complications, time with ICP > 20 mmHg, time with cerebral perfusion pressure (CPP) < 40 mmHg and 12-month Glasgow Outcome Scale-Extended Pediatrics (GOSE-Peds) scores. Association of outcomes with MMM reporting was investigated using the Wilcoxon rank-sum test or Fisher's exact test, as appropriate.ResultsEighty-five children with TBI underwent MMM over 6 years, among which 18 underwent daily MMM reporting over a 21-month period. Clinical decision-making influenced by MMM reporting included timing of neuroimaging (100.0%), ICP monitoring discontinuation (100.0%), timing of extubation trials of surviving patients (100.0%), body repositioning (11.1%), paralytic therapy (16.7%), hyperosmolar therapy (22.2%), pentobarbital therapy (33.3%), provocative cerebral autoregulation testing (16.7%), adjustments in CPP thresholds (16.7%), adjustments in PaCO2 thresholds (11.1%), neurosurgical interventions (16.7%) and neurologic prognostication discussions (11.1%). The implementation of MMM reporting was associated with a reduction in ICP monitoring duration (p = 0.0017) and mechanical ventilator duration (p = 0.0018). No significant differences were observed in initial GCS or PRISM III scores, total hospitalization length, PICU hospitalization length, total complications, time with ICP > 20 mmHg, time with CPP < 40 mmHg, use of tier 2 therapy, or 12-month GOS-E Peds scores.ConclusionImplementation of MMM reporting in pediatric TBI management is feasible and can be impactful in tailoring clinical decisions. Prospective work is needed to understand the impact of MMM and MMM reporting systems on functional outcomes and clinical care efficacy.
| S-EPMC8012079 | biostudies-literature
Project description:Systematic review.To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI).An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI.The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved outcomes; however, the quality of evidence was deemed very low due to selection bias. Seven studies reported MRI predictors of neurologic or functional outcomes. There was moderate-quality evidence that longer intramedullary hemorrhage (2 studies) and low-quality evidence that smaller spinal canal diameter at the location of maximal spinal cord compression and the presence of cord swelling are associated with poor neurologic recovery. There was moderate-quality evidence that clinical outcomes are not predicted by SCI lesion length and the presence of cord edema.Certain MRI characteristics appear to be predictive of outcomes in acute SCI, including length of intramedullary hemorrhage (moderate-quality evidence), canal diameter at maximal spinal cord compression (low-quality evidence), and spinal cord swelling (low-quality evidence). Other imaging features were either inconsistently (presence of hemorrhage, maximal canal compromise, and edema length) or not associated with outcomes. The paucity of literature highlights the need for well-designed prospective studies.
| S-EPMC5684848 | biostudies-other
Project description:The goal of this study is to use bulk RNA-sequencing of the right brain hemisphere to observe the effects of TBI in the context of pre-existing meningeal lymphatic dysfunction in mice. We find that pre-existing meningeal lymphatic dysfunction potentiates the inflammatory response to TBI, suggesting an important role for the meningeal lymphatics in injury site drainage and proper recovery.
2020-07-25 | GSE155063 | GEO