Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation

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.

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Corrigendum to “ERK1/2/mTOR/Stat3 pathway-mediated autophagy alleviates traumatic brain injury-induced acute lung injury” [Biochim. Biophys. Acta 1864/5PA(2018) 1663–1674]

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2018.04.003 ◽

2018 ◽

Vol 1864 (6) ◽

pp. 2214

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

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

Science Translational Medicine ◽

10.1126/scitranslmed.3009443 ◽

2014 ◽

Vol 6 (252) ◽

pp. 252ra124-252ra124 ◽

Cited By ~ 59

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.

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

Iranian Journal of Neurosurgery ◽

10.32598/irjns.7.3.3 ◽

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.

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