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Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Ethanol exacerbates post-burn neuroinflammation and gut-brain barrier dysfunction which are associated with
Rachel H McMahan1, Mara R Evans1, Kevin M Najarro1
1Department of Surgery, Division of GI, Trauma and Endocrine Surgery, Alcohol Research Program, and Burn Research Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Acute alcohol intoxication before burn injury worsens neuroinflammation and disrupts the blood-brain barrier (BBB). Ethanol exposure alters the gut microbiome, contributing to these negative effects in burn patients.
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Acute alcohol intoxication is linked to increased complications and inflammation after burn injuries.
- The specific effects of ethanol on neuroinflammation and blood-brain barrier (BBB) integrity post-burn are not well understood.
- Ethanol's impact on the gut microbiome and its role in exacerbating neuroinflammation require further investigation.
Purpose of the Study:
- To investigate the impact of acute ethanol exposure prior to burn injury on neuroinflammation and BBB integrity.
- To determine if ethanol exposure disrupts intestinal and cerebrovascular barriers and alters the gut microbiome.
- To elucidate the mechanisms linking ethanol, burn injury, and neuroinflammation.
Main Methods:
- A murine model was used, administering acute ethanol 30 minutes before burn injury.
- Brain tissue was analyzed for inflammatory markers, microglial activation, and BBB permeability (albumin accumulation).
- Intestinal barrier function was assessed via bacterial translocation and lipopolysaccharide (LPS) levels; fecal microbiome composition was analyzed using 16S rRNA sequencing.
Main Results:
- Ethanol exposure prior to burn injury significantly elevated brain expression of inflammatory genes (Ccl2, Tnfa, S100a8) and enhanced microglial activation.
- Ethanol exacerbated intestinal barrier dysfunction, evidenced by increased bacterial translocation and LPS levels.
- BBB permeability was significantly increased in ethanol-exposed mice, with a notable expansion of Escherichia species in the gut microbiome correlating with brain inflammation.
Conclusions:
- Ethanol exposure before burn injury potentiates neuroinflammation and disrupts BBB integrity.
- Gut microbial dysbiosis is associated with ethanol-induced neuroinflammation following burn injury.
- The gut-brain axis plays a critical role in the heightened neuroinflammation observed in intoxicated burn patients, suggesting potential therapeutic targets.
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