Non-severe burn injury leads to sustained molecular changes in the brain in a murine model
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PROVIDER: PRJNA1303590 | ENA |
REPOSITORIES: ENA
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Project description:Background: Paediatric burn patients, including those with non-severe burns, have an increased risk of admission to hospital for mental health conditions for many years after the burn, even in children too young at the time of the burn to remember the incident. This study aimed to investigate the long-term physiological impact of non-severe burn injuries and non-burn trauma (NBT) on the brain in mice to understand whether there is a sustained impact of such injuries on the brain that may be linked to the increased mental health morbidity observed in patients. Methods: Mice were exposed to either a non-severe burn injury, an excision injury of the same size (equivalent non-burn trauma), or a sham procedure. Behavioural tests were conducted at multiple timepoints to measure anxiety and depression-like behaviour. Mice were euthanised three months after the injury, and plasma and brain tissue, including the hippocampus and prefrontal cortex, were isolated and examined using RNA sequencing, mass spectrometry and nuclear magnetic resonance (NMR) to identify transcriptomic and metabolomic changes. Results: A significant change in behaviour was observed with an increase in sucrose consumption three months after injury in the burn group compared to sham. Significant changes in the transcriptome were identified in some brain regions at 3 months after burn trauma compared to the sham group. Differentially expressed genes associated with inflammatory and immune functions were identified in the burn group compared to controls. Significant changes were also observed in the lipid profile and tryptophan catabolites in the brain after burn trauma compared to sham. Conclusion: Sustained changes in the transcriptome and metabolome were identified in a mouse model of non-severe burns, supporting a likely sustained pro-inflammatory environment in the brain after this type of injury. The potential link between these changes and the poor long-term mental health outcomes observed in paediatric burn patients requires further investigation.
2025-08-14 | GSE304956 | GEO
Project description:Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response severe injury, with little in the literature reported on impact of non-severe injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of non-severe burn injury, longitudinal plasma was collected from adults (n=35) who presented at hospital with a non-severe burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from non-burn control participants (n=14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoproteins signatures and 852 lipid species from across 20 subclasses.
Multivariate data modelling (Orthogonal projection to latent structures-discriminate analysis) revealed alterations in lipoprotein and lipid metabolism when comparing baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value <1.0e-4), low density lipoprotein-2 subfractions (Variable importance in projection score; VIP >6.83e-1) and monoacyglyceride (20:4)(p-value <1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP >7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines.
The results indicate a persistant systemic metabolic phenotype that occurs even in cases of non-severe burn injury. The phenotype is indicative of an accute inflammatory profile which continues to be sustained post-injury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have elevated incidence post- burn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalise intervention strtegies and improve acute care, reducing risk of chronic co-morbidity.
2023-07-19 | MSV000092486 | MassIVE
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days. 114 arrays for 57 patients (2 time points per patient) and 63 arrays for 63 healthy controls.
2010-06-16 | E-GEOD-19743 | biostudies-arrayexpress
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days.
2010-06-03 | GSE19743 | GEO
Project description:Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012-2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (FDR≤0.1) by burn injury severity, patients were grouped by total body surface area (TBSA) above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (IQR, 30.5-58.5) years, and TBSA of 20% (11-34%). Thirty-five patients had %TBSA injury ≥20%, and this group experienced greater mortality (26% vs. 3%, p=0.008). Comparative analysis of genes from patients with </≥20% TBSA revealed 1505, 613, 380, 63, 1357, and 954 differentially expressed genes at hours 0, 2, 4, 8, 12 and 24 respectively. Pathway analysis revealed an initial upregulation in several immune/inflammatory pathways within the ≥20% TBSA groups followed by shutdown. Severe burn injury is associated with an early proinflammatory immune response followed by shutdown of these pathways. Examination of the immunoinflammatory response to burn injury through differential gene regulation and associated immune pathways by injury severity may identify mechanistic targets for future intervention.
2021-10-31 | GSE182616 | GEO
Project description:scRNA and snATAC sequencing of cells harvested from the tendon injury site after a severe burn/tenotomy injury in Hoxa11 lineage traced mice allowed for differentation tracing of MSCs located in zeugopod after severe heterotopic ossification inducing injury. The use of immobilization also allowed us to determine the effects of limb immoblization on MSCs during aberrant wound healing.
2020-06-30 | GSE150995 | GEO
Project description:Introduction Severe injury, including burn trauma, leads to profound immune dysfunction, yet the mechanisms driving these changes remain incompletely defined. This lack of understanding has hindered efforts to modulate the immune response effectively. Additionally, a clear biomarker profile to guide clinicians in identifying burn patients at high risk for poor clinical outcomes is lacking. Extracellular vesicles (EVs) have emerged as novel mediators of immune dysfunction in various pathologies. Prior studies in mouse models have demonstrated that plasma EVs increase following burn injury and contribute to immune dysfunction. Furthermore, EVs have potential as biomarkers for predicting extended hospital stays in burn patients. This study hypothesizes that human EVs, purified early and late after burn injury, will exhibit immune reprogramming effects similar to those observed in mice and that specific EV protein cargo may serve as biomarkers of immune and physiological responses to burn injury. Methods EVs were isolated from the plasma of burn-injury patients at early (<72h) and late (≥14 days) time points post-injury. Using unbiased immune transcriptome and bioinformatic causal network analyses, the immunomodulatory effects of these EVs were assessed in human THP-1 macrophages. Mass spectrometry-based quantitative proteomics and pathway analyses were conducted to characterize the protein cargo of EVs from both human and mouse models at different post-burn phases. Results Early post-burn human EVs induced significant immune reprogramming in macrophages, increasing pro-inflammatory signaling while suppressing anti-inflammatory pathways. In contrast, late post-burn EVs exhibited an immunosuppressive profile, with downregulation of pro-inflammatory pathways and upregulation of anti-inflammatory signaling. Proteomic analyses revealed that human and mouse EVs contained unique and overlapping protein cargo across different time points. At day 7 post-burn, mouse EVs were enriched in circulation/complement and neuronal proteins, whereas by day 14, reductions in membrane and metabolism-associated proteins were observed. Similarly, in human EVs at 14 days post-burn, increased levels of circulation/complement, immune, and transport proteins were detected. Conclusions EVs from burn-injury patients at distinct time points differentially modulate immune responses in macrophages, mirroring the temporal immune phenotypes observed in clinical settings. These findings suggest that EV-macrophage interactions play a crucial role in burn-induced immune dysfunction and highlight the potential of EV protein cargo as biomarkers for immune status and patient outcomes following burn injury.
2025-05-21 | PXD062615 | Pride
Project description:Severe burn injury is a one of the most devastating forms of trauma with over 1.1 million burns each year requiring medical attention in the United States. Deaths from burn injury are commonly caused by immune-related sequelae such as pneumonia, organ failure and other opportunistic bacterial infections. Though there have been numerous studies to assess the immunological dysfunction associated with burn injury, there have yet to be a predictive biomarker, that can be used to assess high risk patients and their outcomes. We hypothesized that circulating extracellular vesicles (EVs) released early after burn injury would promote activate peripheral macrophages and specific cargo could be used as a biomarker to identify at-risk patients. To test this hypothesis, we assessed the immune consequences of adoptive transfer of EVs isolated after burn injury in vitro and used unbiased proteomic on EVs from mouse models and human burn patients from the UNC Jaycee Burn Center. Findings here suggest EVs serve as mediators of immune dysfunction and potential biomarkers.
2022-02-16 | PXD028515 | Pride
Project description:A dysregulated immune response after severe burn injury is associated with detrimental short and long-term clinical outcomes. Key changes to gene expression within the first 24 h after burn injury have been identified, but longitudinal data is lacking. Therefore, this study aims to characterize gene expression during the first 3 weeks after burn injury and identify specific genes and pathways associated with distinct clinical outcomes. Patients presenting within 4 h of injury had blood RNA isolated for microarray gene expression at admission and set timepoints to 21 days. Inter- and intra-group comparisons were performed between 4 groups (G1 died within 7 days; G2 died after 7 days; G3 discharged after 7 days; and G4 discharged within 7 days). A total of 17 289 transcripts were quantified from 116 patients. At admission, there were 110, 80, and 31 differentially expressed genes in G1, G2, and G3, respectively, compared to G4, and were largely nonoverlapping. Longitudinal intra-group analyses also showed distinct group- and time-dependent patterns. Upregulation of genes and pathways related to the innate immune response and unfolded protein response predominated during early time points, while persistent upregulation of coagulation pathways and downregulation of immune-related pathways were identified days to weeks following injury. Overall, burn injury induces widespread transcriptomic responses, with larger and more sustained changes observed in patients with worse clinical outcomes. These gene expression signatures reveal underlying molecular mechanisms that occur immediately following injury and may have prognostic and diagnostic utility in the care of burn-injured patients.
2025-05-28 | GSE269523 | GEO
Project description:Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. Burn injury patients commonly develop chronic neurological disorders but the long-lasting impacts of burn injuries on neurons and glia in the brain is unknown. Whole transcriptome RNA-sequencing from cortical excitatory neurons, inhibitory neurons, astrocytes and microglia showed very few changes to the expression of genes with known functions five weeks following a non-severe burn injury in adult mice. However, genes related to GABA-A receptors in excitatory neurons and several cellular functions in microglia was found to be to differentially expressed in burn injured mice. These findings shed light on the long-term effect of burn injuries on the brain and may help identify potential therapeutic targets and windows to prevent neurological dysfunction in burn patients.
2024-02-15 | GSE229384 | GEO