scholarly journals Human Lung Cell Pyroptosis Following Traumatic Brain Injury

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 69 ◽  
Author(s):  
Nadine Kerr ◽  
Juan de Rivero Vaccari ◽  
Oliver Umland ◽  
M. Bullock ◽  
Gregory Conner ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Endothelial Cell ◽  
Brain Injury ◽  
Lung Injury ◽  
Critical Role ◽  
Gunshot Wounds ◽  
Extracellular Vesicle ◽  
Inflammasome Activation ◽  
Trauma Patients ◽  
Severe Tbi

Approximately 30% of traumatic brain injured patients suffer from acute lung injury or acute respiratory distress syndrome. Our previous work revealed that extracellular vesicle (EV)-mediated inflammasome signaling plays a crucial role in the pathophysiology of traumatic brain injury (TBI)-induced lung injury. Here, serum-derived EVs from severe TBI patients were analyzed for particle size, concentration, origin, and levels of the inflammasome component, an apoptosis-associated speck-like protein containing a caspase-recruiting domain (ASC). Serum ASC levels were analyzed from EV obtained from patients that presented lung injury after TBI and compared them to EV obtained from patients that did not show any signs of lung injury. EVs were co-cultured with lung human microvascular endothelial cells (HMVEC-L) to evaluate inflammasome activation and endothelial cell pyroptosis. TBI patients had a significant increase in the number of serum-derived EVs and levels of ASC. Severe TBI patients with lung injury had a significantly higher level of ASC in serum and serum-derived EVs compared to individuals without lung injury. Only EVs isolated from head trauma patients with gunshot wounds were of neural origin. Delivery of serum-derived EVs to HMVEC-L activated the inflammasome and resulted in endothelial cell pyroptosis. Thus, serum-derived EVs and inflammasome proteins play a critical role in the pathogenesis of TBI-induced lung injury, supporting activation of an EV-mediated neural-respiratory inflammasome axis in TBI-induced lung injury.

scholarly journals miR-29a-5p Alleviates Traumatic Brain Injury (TBI)-Induced Permeability Disruption Via Regulating NLRP3 Pathway

2021 ◽  
Author(s):  
Aijun Zhang ◽  
Youming Lu ◽  
Lei Yuan ◽  
Pengqi Zhang ◽  
Dongdong Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Endothelial Cell ◽  
Brain Injury ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Promising Strategy ◽  
Pathway Activation ◽  
Nlrp3 Expression

Abstract Blood-brain barrier (BBB) dysfunction is presented during traumatic brain injury (TBI) and is dependent upon the activation of the NLRP3/Caspase-1 inflammasome pathway. MicroRNA (miRNA) was proved to inhibit signaling pathway activation by targeting gene expression and we predicated in the database that miR-29a targets to NLRP3. Herein, this study aims to define the regulating role of miR-29a in NLRP3 expression and NLRP3/Caspase-1 inflammasome activation in TBI-induced BBB dysfunction. Our results indicated that miR-29a-5p alleviates TBI-induced the increased permeability of endothelial cell and BBB via suppressing NLRP3 expression and NLRP3/Caspase-1 inflammasome activation, providing a promising strategy for relieving TBI via inhibiting NLRP3/Caspase-1 inflammasome activation.

Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children

Neurosurgery ◽  
2011 ◽  
Vol 68 (3) ◽  
pp. 588-600 ◽  
Author(s):  
Charles S. Cox ◽  
James E. Baumgartner ◽  
Matthew T. Harting ◽  
Laura L. Worth ◽  
Peter A. Walker ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Bone Marrow ◽  
Renal Function ◽  
Brain Injury ◽  
Lung Injury ◽  
Mononuclear Cell ◽  
Severe Traumatic Brain Injury ◽  
Cerebral Hemodynamics ◽  
Hepatic Enzymes ◽  
Severe Tbi

Abstract BACKGROUND: Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection. OBJECTIVE: To determine whether autologous BMMNCs are a safe treatment for severe TBI in children. METHODS: Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6 × 106 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures. RESULTS: All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability. CONCLUSION: Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.

scholarly journals Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: the multicentre randomised controlled OXY-TC trial study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e040550
Author(s):  
Jean-Francois Payen ◽  
Marion Richard ◽  
Gilles Francony ◽  
Gérard Audibert ◽  
Emmanuel L Barbier ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Life Assessment ◽  
Secondary Outcome ◽  
Trauma Patients ◽  
Brain Tissue Oxygenation ◽  
Severe Tbi ◽  
Randomised Controlled ◽  
The Impact

IntroductionIntracranial hypertension is considered as an independent risk factor of mortality and neurological disabilities after severe traumatic brain injury (TBI). However, clinical studies have demonstrated that episodes of brain ischaemia/hypoxia are common despite normalisation of intracranial pressure (ICP). This study assesses the impact on neurological outcome of guiding therapeutic strategies based on the monitoring of both brain tissue oxygenation pressure (PbtO2) and ICP during the first 5 days following severe TBI.Methods and analysisMulticentre, open-labelled, randomised controlled superiority trial with two parallel groups in 300 patients with severe TBI. Intracerebral monitoring must be in place within the first 16 hours post-trauma. Patients are randomly assigned to the ICP group or to the ICP + PbtO2 group. The ICP group is managed according to the international guidelines to maintain ICP≤20 mm Hg. The ICP + PbtO2 group is managed to maintain PbtO2 ≥20 mm Hg in addition to the conventional optimisation of ICP. The primary outcome measure is the neurological status at 6 months as assessed using the extended Glasgow Outcome Scale. Secondary outcome measures include quality-of-life assessment, mortality rate, therapeutic intensity and incidence of critical events during the first 5 days. Analysis will be performed according to the intention-to-treat principle and full statistical analysis plan developed prior to database freeze.Ethics and disseminationThis study has been approved by the Institutional Review Board of Sud-Est V (14-CHUG-48) and from the National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des produits de santé) (141 435B-31). Results will be presented at scientific meetings and published in peer-reviewed publications.The study was registered with ClinTrials NCT02754063 on 28 April 2016 (pre-results).

scholarly journals Plasma glutamate–modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury–induced acute lung injury

2013 ◽  
Vol 210 (4) ◽  
pp. 839-851 ◽  
Author(s):  
Shuang-Shuang Dai ◽  
Hao Wang ◽  
Nan Yang ◽  
Jian-Hong An ◽  
Wei Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Metabotropic Glutamate Receptor ◽  
White Blood Cells ◽  
Protective Role ◽  
Lung Damage ◽  
Severe Tbi ◽  
Proinflammatory Effect

The bone marrow–derived cell (BMDC)–associated inflammatory response plays a key role in the development of acute lung injury (ALI). Activation of adenosine A2A receptor (A2AR) is generally considered to be antiinflammatory, inhibiting BMDC activities to protect against ALI. However, in the present study, we found that in a mouse model of neurogenic ALI induced by severe traumatic brain injury (TBI), BMDC A2AR exerted a proinflammatory effect, aggravating lung damage. This is in contrast to the antiinflammatory effect observed in the mouse oleic acid–induced ALI model (a nonneurogenic ALI model.) Moreover, the A2AR agonist CGS21680 aggravated, whereas the antagonist ZM241385 attenuated, the severe TBI-induced lung inflammatory damage in mice. Further investigation of white blood cells isolated from patients or mouse TBI models and of cultured human or mouse neutrophils demonstrated that elevated plasma glutamate after severe TBI induced interaction between A2AR and the metabotropic glutamate receptor 5 (mGluR5) to increase phospholipase C–protein kinase C signaling, which mediated the proinflammatory effect of A2AR. These results are in striking contrast to the well-known antiinflammatory and protective role of A2AR in nonneurogenic ALI and indicate different therapeutic strategies should be used for nonneurogenic and neurogenic ALI treatment when targeting A2AR.

scholarly journals Severe traumatic brain injury and hypotension is a frequent and lethal combination in mountain trauma patients – an analysis of the International Alpine Trauma Registry

2020 ◽  
Author(s):  
Simon Rauch ◽  
Matilde Marzolo ◽  
Tomas Dal Cappello ◽  
Mathias Ströhle ◽  
Peter Mair ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Base Excess ◽  
Trauma Registry ◽  
Trauma Patients ◽  
Abbreviated Injury Scale ◽  
Hospital Arrival ◽  
Severe Tbi ◽  
Head Neck ◽  
Group 1

Abstract Background: Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multi-trauma in remote and mountainous areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension.Methods: Data from the International Alpine Trauma Registry including mountain multi-trauma patients (ISS≥16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP <110 mmHg on hospital arrival.Results: A total of 287 patients were included. Fifty (17%) had TBI and hypotension, 92 (32%) suffered TBI without hypotension and 145 (51%) patients did not have TBI. Patients in group 1 were more severely injured (mean ISS 43.1±17.4 vs 33.3±15.3 vs 26.2±18.1 for group 1 vs 2 vs 3, respectively, p<0.001). Mean SBP on hospital arrival was 83.1±12.9 vs 132.5±19.4 vs 119.4±25.8 mmHg (p<0.001) despite patients in group 1 received more fluids. Patients in group 1 had higher INR, lower haemoglobin and lower base excess (p<0.001). The rate of hypothermia on hospital arrival was different between the groups (p=0.029). Patients in group 1 had the highest mortality (24% vs 10% vs 1%, p<0.001).Conclusion: Multi-trauma in the mountains goes along with severe TBI in almost 50%. One third of patients with TBI is hypotensive on hospital arrival and this is associated with a worse outcome. No single variable or set of variables easily obtainable at scene was able to predict admission hypotension in TBI patients.

scholarly journals miR-142-3p Expression Is Predictive for Severe Traumatic Brain Injury (TBI) in Trauma Patients

2020 ◽  
Vol 21 (15) ◽  
pp. 5381
Author(s):  
Cora Rebecca Schindler ◽  
Mathias Woschek ◽  
Jan Tilmann Vollrath ◽  
Kerstin Kontradowitz ◽  
Thomas Lustenberger ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Predictive Biomarkers ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Predictive Values ◽  
Risk Of Mortality ◽  
Affected Tissue ◽  
Severe Tbi ◽  
Injured Patients

Background: Predictive biomarkers in biofluids are the most commonly used diagnostic method, but established markers in trauma diagnostics lack accuracy. This study investigates promising microRNAs (miRNA) released from affected tissue after severe trauma that have predictive values for the effects of the injury. Methods: A retrospective analysis of prospectively collected data and blood samples of n = 33 trauma patients (ISS ≥ 16) is provided. Levels of miR-9-5p, -124-3p, -142-3p, -219a-5p, -338-3p and -423-3p in severely injured patients (PT) without traumatic brain injury (TBI) or with severe TBI (PT + TBI) and patients with isolated TBI (isTBI) were measured within 6 h after trauma. Results: The highest miR-423-3p expression was detected in patients with severe isTBI, followed by patients with PT + TBI, and lowest levels were found in PT patients without TBI (2−∆∆Ct, p = 0.009). A positive correlation between miR-423-3p level and increasing AIShead (p = 0.001) and risk of mortality (RISC II, p = 0.062) in trauma patients (n = 33) was found. ROC analysis of miR-423-3p levels revealed them as statistically significant to predict the severity of brain injury in trauma patients (p = 0.006). miR-124-3p was only found in patients with severe TBI, miR-338-3p was shown in all trauma groups. miR-9-5p, miR-142-3p and miR-219a-5p could not be detected in any of the four groups. Conclusion: miR-423-3p expression is significantly elevated after isolated traumatic brain injury and predictable for severe TBI in the first hours after trauma. miR-423-3p could represent a promising new biomarker to identify severe isolated TBI.

Is Routine Continuous EEG for Traumatic Brain Injury Beneficial?

2017 ◽  
Vol 83 (12) ◽  
pp. 1433-1437 ◽  
Author(s):  
Lia Aquino ◽  
Christopher Y. Kang ◽  
Megan Y. Harada ◽  
Ara Ko ◽  
Amy Do-nguyen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Injury Severity ◽  
Trauma Patients ◽  
Injury Score ◽  
Increased Risk ◽  
Continuous Eeg ◽  
Severe Tbi ◽  
Level I ◽  
Abbreviated Injury Score

Severe traumatic brain injury (TBI) is associated with increased risk for early clinical and sub-clinical seizures. The use of continuous electroencephalography (cEEG) monitoring after TBI allows for identification and treatment of seizures that may otherwise occur undetected. Benefits of “routine” cEEG after TBI remain controversial. We examined the rate of subclinical seizures identified by cEEG in TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma patients with moderate to severe TBI (head Abbreviated Injury Score ≥3) who received cEEG within seven days of admission between October 2011 and May 2015. Demographics, clinical data, injury severity, and costs were recorded. Clinical characteristics were compared between those with and without seizures as identified by cEEG. A total of 106 TBI patients with moderate to severe TBI received a cEEG during the study period. Most were male (74%) with a mean age of 55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of patients. Ninety-three per cent were on antiseizure prophylaxis at the time of cEEG. Patients who had subclinical seizures were significantly older than their counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were similar in both groups. Of all TBI patients who were monitored with cEEG, seizures were identified in only 3.8 per cent. Seizures were more likely to occur in older patients with severe head injury. Given the high cost of routine cEEG and the low incidence of subclinical seizures, we recommend cEEG monitoring only when clinically indicated.

scholarly journals Severe traumatic brain injury and hypotension is a frequent and lethal combination in multiple trauma patients in mountain areas – an analysis of the prospective international Alpine Trauma Registry

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Simon Rauch ◽  
◽  
Matilde Marzolo ◽  
Tomas Dal Cappello ◽  
Mathias Ströhle ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Multiple Trauma ◽  
Trauma Registry ◽  
Trauma Patients ◽  
Mountain Areas ◽  
Hospital Arrival ◽  
Severe Tbi ◽  
Multiple Trauma Patients ◽  
Group 1

Abstract Background Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multiple trauma in mountain areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension. Methods Data from the prospective International Alpine Trauma Registry including mountain multiple trauma patients (ISS ≥ 16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP < 110 mmHg on hospital arrival. Results A total of 287 patients were included. Fifty (17%) had TBI and hypotension, 92 (32%) suffered TBI without hypotension and 145 (51%) patients did not have TBI. Patients in group 1 were more severely injured (mean ISS 43.1 ± 17.4 vs 33.3 ± 15.3 vs 26.2 ± 18.1 for group 1 vs 2 vs 3, respectively, p < 0.001). Mean SBP on hospital arrival was 83.1 ± 12.9 vs 132.5 ± 19.4 vs 119.4 ± 25.8 mmHg (p < 0.001) despite patients in group 1 received more fluids. Patients in group 1 had higher INR, lower haemoglobin and lower base excess (p < 0.001). More than one third of patients in group 1 and 2 were hypothermic (body temperature < 35 °C) on hospital arrival while the rate of admission hypothermia was low in patients without TBI (41% vs 35% vs 21%, for group 1 vs 2 vs 3, p = 0.029). The rate of hypothermia on hospital arrival was different between the groups (p = 0.029). Patients in group 1 had the highest mortality (24% vs 10% vs 1%, p < 0.001). Conclusion Multiple trauma in the mountains goes along with severe TBI in almost 50%. One third of patients with TBI is hypotensive on hospital arrival and this is associated with a worse outcome. No single variable or set of variables easily obtainable at scene was able to predict admission hypotension in TBI patients.

scholarly journals Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Spencer Flynn ◽  
Jacqueline Leete ◽  
Pashtun Shahim ◽  
Cassandra Pattinson ◽  
Vivian A. Guedes ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Injury Severity ◽  
Extracellular Vesicle ◽  
Individual Variability ◽  
Acidic Protein ◽  
Neurofilament Light ◽  
Ultrasensitive Assay ◽  
Severe Tbi

AbstractTraumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale–Extended (GOS-E) score (p’s < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.

scholarly journals Enoxaparin Attenuates Acute Lung Injury and Inflammasome Activation after Traumatic Brain Injury

2020 ◽  
Author(s):  
Nadine A. Kerr ◽  
Juan Pablo de Rivero Vaccari ◽  
Cailey Weaver ◽  
W. Dalton Dietrich ◽  
Tahir Ahmed ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Inflammasome Activation
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