Pediatric anesthesia & critical care

The molecular architecture of severe pediatric traumatic brain injury: integrated omics reveal therapeutic pathways

Crit CarePublished Prospective observational cohort study

Authors' conclusion

Despite the heterogeneity in injury mechanisms and clinical presentations, our findings reveal a convergent host response, characterized by shared transcriptomic and metabolic signatures across all time points.

Study context

Population
Children with severe traumatic brain injury (TBI) (median age 13.1 years, median Glasgow Coma Scale (GCS) 3, median Injury Severity Score (ISS) 29) in the pediatric intensive care unit (PICU), enrolled May 2022–November 2023
Exposure
Severe pediatric TBI vs sex and age-matched controls
  • TBIn = 17
Outcome
Transcriptomic and metabolomic signatures over 9 days in PICU
Follow-up
Three timepoints over nine days
Methodological detailslongitudinal, integrated multi-omics (whole-blood transcriptomics, serum metabolomics), sex and age-matched controls
  • Longitudinal
  • Integrated multi-omics (whole-blood transcriptomics, serum metabolomics)
  • Sex and age-matched controls

Main finding

As reported in the abstract

  • Overlap in transcriptomic and metabolic signatures at each timepoint despite heterogeneity of mechanism and presentation
  • Acute phase: inflammatory and immune activation, metabolic dysregulation, disturbance of the gut-brain axis
  • Early T-cell infiltration markers (TRAV35, ANXA2R) highly correlated with GCS
  • Lysophosphatidylcholine 18:0 highly correlated with NK-cell activation
  • Gut metabolites (e.g. indole-3-propionic acid) and RNA signatures of gut flora elevated in blood early after TBI
  • Putrescine elevation at time point one highly correlates with Day 9 RBC stimulation
  • At Day 9, multiple lipid species associated with LOS and GOS-E Peds
  • By Day 9, incomplete recovery of metabolome and transcriptome, with TBI-specific IGH, IGK and IGL clonal expansion

Observational data: associations, not effects.

Original publication

The molecular architecture of severe pediatric traumatic brain injury: integrated omics reveal therapeutic pathways. Crit Care. Published 9 December 2025. doi:10.1186/s13054-025-05789-7

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