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 Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury

2017 ◽  
Vol 41 (5) ◽  
pp. 2037-2044 ◽  
Author(s):  
Yuan Liu ◽  
Junyu Lu ◽  
Xiaoya Wang ◽  
Liu Chen ◽  
Su Liu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Lavage Fluid ◽  
Protective Role ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Tnf Α ◽  
Weight Drop

Background: Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. Methods: In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis. Results: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung. Conclusions: We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients.

Class B Scavenger Receptors BI and BII Protect Against LPS-induced Acute Lung Injury in Mice by Mediating LPS Clearance

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Protective Role ◽  
Lung Damage ◽  
Wild Type ◽  
Class B ◽  
Anti Inflammatory

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

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 The HMGB1-RAGE axis mediates traumatic brain injury–induced pulmonary dysfunction in lung transplantation

2014 ◽  
Vol 6 (252) ◽  
pp. 252ra124-252ra124 ◽  
Author(s):  
Daniel J. Weber ◽  
Adam S. A. Gracon ◽  
Matthew S. Ripsch ◽  
Amanda J. Fisher ◽  
Bo M. Cheon ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Lung Transplantation ◽  
Inflammatory Responses ◽  
Pulmonary Dysfunction ◽  
Wild Type ◽  
Hmgb1 Protein ◽  
Lung Dysfunction

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE−/−) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs’ ability to expand), all of which were attenuated in RAGE−/−mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE−/−TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.

scholarly journals Incidence and Outcomes of Acute Lung Injury in Patients With Isolated Traumatic Brain Injury

2021 ◽  
Vol 7 (3) ◽  
pp. 139-146
Author(s):  
Siamak Rimaz ◽  
◽  
Seyyed Mahdi Zia Ziabari ◽  
Neshat Jabbari ◽  
Zahra Pourmohammadi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Brain Damage ◽  
Study Data ◽  
Cerebral Injury ◽  
Age Group ◽  
Cross Sectional ◽  
Motorcycle Accident

Background and Aim: Traumatic Brain Injury (TBI) is an essential cause of morbidity and mortality worldwide. TBI patients frequently encounter lung complications, such as Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS), which is associated with poor clinical outcome because hypoxia causes additional injury to the brain. This study aimed to evaluate the frequency of ALI in patients with TBI and its consequences. Methods and Materials/Patients: In this descriptive cross-sectional study, data from all records of patients admitted to Poursina Hospital’s ICU (emergency and neurosurgery ICU) in 20 18-2019 were used. The evaluated data included age, gender, type of head trauma mechanism, kind of brain injury based on CT scan findings, the severity of brain injury based on Glasgow Coma Scale (GCS), underlying diseases, mean head AIS score, the number of pack cell units injected, as well as bilateral pulmonary infiltration in favor of ALI and brain injury. Results: Only 81 of the 557 TBI cases met the inclusion criteria of the present study. The highest frequency of ALI following TBI was observed on the first day of hospitalization, in men (0.41%) in the age group of 40-50 years (7%) with severe brain damage (6%) and subdural hematoma (12%), following a motorcycle accident, cars, as well as on the third day of hospitalization were seen in men (43.8%) with the age group of 20-30 years (55%) with severe brain damage (42%) and intra-parenchymal bleeding (57%), following a motorcycle accident. In addition, no significant correlation was detected between the incidence of ALI and mortality, the duration of hospitalization, GCS, mean head AIS score, or the extent of received blood units in our study. Conclusion: According to the obtained findings, men aged between 20 and 30 years with severe cerebral injury, epidural hematoma and a motorcycle accident presented the highest rate of progression toward ALI in the first to third days of hospitalization.

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 ERK1/2/mTOR/Stat3 pathway-mediated autophagy alleviates traumatic brain injury-induced acute lung injury

2018 ◽  
Vol 1864 (5) ◽  
pp. 1663-1674 ◽  
Author(s):  
Xiupeng Xu ◽  
Tongle Zhi ◽  
Honglu Chao ◽  
Kuan Jiang ◽  
Yinlong Liu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Stat3 Pathway

Genetic Ablation of Nrf2 Enhances Susceptibility to Acute Lung Injury After Traumatic Brain Injury in Mice

2009 ◽  
Vol 234 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Wei Jin ◽  
Handong Wang ◽  
Yan Ji ◽  
Lin Zhu ◽  
Wei Yan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Genetic Ablation
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