Alcohol (Fayetteville, N.Y.) · 2026
Ethanol exacerbates post-burn neuroinflammation and gut-brain barrier dysfunction which are associated with microbiome changes.
СтатьяОбзорПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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McMahan Rachel H, Evans Mara R, Najarro Kevin M, Frank Daniel N, Basak Jacob M, Kovacs Elizabeth J
Аннотация
BACKGROUND: Acute alcohol intoxication at the time of burn injury is associated with increased morbidity and worsened systemic inflammation. While the detrimental effects of ethanol on peripheral organs after burn injury are well established, its impact on neuroinflammation and the blood-brain barrier (BBB) integrity remains to be defined. We hypothesized that ethanol exposure prior to burn injury heightens neuroinflammation through disruption of intestinal and cerebrovascular barriers and alterations in the gut microbiome.
METHODS: Using a clinically relevant murine model, mice received acute ethanol exposure 30 min prior to burn injury. Brains were analyzed 24 h later for inflammatory gene and protein expression. Microglial activation was determined by IBA-1 immunofluorescence and quantitative PCR of isolated microglia. Intestinal barrier dysfunction was evaluated by bacterial translocation to mesenteric lymph nodes (MLN) and serum lipopolysaccharide (LPS) levels. BBB permeability was assessed in brain tissue by albumin accumulation. Fecal microbiome composition was characterized by 16S rRNA gene sequencing.
RESULTS: Burn injury alone induced morphological evidence of reactivity, yet did not significantly increase brain pro-inflammatory cytokine transcription. In contrast, ethanol exposure prior to burn injury elevated brain expression of Ccl2, Tnfa, and S100a8. Isolated microglia from the brains of mice given ethanol and burn injury exhibited enhanced expression of Ccl2 compared to burn alone. Ethanol exposure also resulted in an 8-fold increase in bacterial translocation to MLNs and a 5-fold increase in brain albumin levels, indicating exacerbated intestinal and BBB permeability. Microbiome analysis revealed expansion of Escherichia species in mice subjected to ethanol and burn injury, which positively correlated with brain S100a8 expression.
CONCLUSIONS: Ethanol exposure prior to burn injury potentiates neuroinflammation, enhances microglial pro-inflammatory reactivity, disrupts BBB integrity, and is associated with gut microbial dysbiosis. These findings implicate dysregulation of the gut-brain axis as a mechanistic contributor to worsened neuroinflammation in intoxicated burn injury and identify potential therapeutic targets to mitigate neurologic complications in this high-risk population.
METHODS: Using a clinically relevant murine model, mice received acute ethanol exposure 30 min prior to burn injury. Brains were analyzed 24 h later for inflammatory gene and protein expression. Microglial activation was determined by IBA-1 immunofluorescence and quantitative PCR of isolated microglia. Intestinal barrier dysfunction was evaluated by bacterial translocation to mesenteric lymph nodes (MLN) and serum lipopolysaccharide (LPS) levels. BBB permeability was assessed in brain tissue by albumin accumulation. Fecal microbiome composition was characterized by 16S rRNA gene sequencing.
RESULTS: Burn injury alone induced morphological evidence of reactivity, yet did not significantly increase brain pro-inflammatory cytokine transcription. In contrast, ethanol exposure prior to burn injury elevated brain expression of Ccl2, Tnfa, and S100a8. Isolated microglia from the brains of mice given ethanol and burn injury exhibited enhanced expression of Ccl2 compared to burn alone. Ethanol exposure also resulted in an 8-fold increase in bacterial translocation to MLNs and a 5-fold increase in brain albumin levels, indicating exacerbated intestinal and BBB permeability. Microbiome analysis revealed expansion of Escherichia species in mice subjected to ethanol and burn injury, which positively correlated with brain S100a8 expression.
CONCLUSIONS: Ethanol exposure prior to burn injury potentiates neuroinflammation, enhances microglial pro-inflammatory reactivity, disrupts BBB integrity, and is associated with gut microbial dysbiosis. These findings implicate dysregulation of the gut-brain axis as a mechanistic contributor to worsened neuroinflammation in intoxicated burn injury and identify potential therapeutic targets to mitigate neurologic complications in this high-risk population.