Multi-Organ Inflammatory and Endocrine Crosstalk Shapes the Early Brain Response to Combined Burn and Blast Injury

By comparison, the consequences of combined burn and traumatic brain injury are largely unknown, despite their frequent co-occurrence in military settings and the potential for synergistic effects on the central nervous system. To address this gap, we utilized a murine model combining blast-induced brain injury with a 15% total body surface area flame burn to approximate a common combat-related trauma.

Burn injury alone induced systemic cytokine secretion, hematopoietic reprioritization, and anemia, whereas the overlapping brain injury did not further exacerbate systemic effects but magnified brain transcriptional responses. Bulk RNA-seq profiling at 6 hours post-injury revealed that inflammatory and glucocorticoid-responsive pathways were among the most enriched after combined injury, implicating coordinated immune and neuroendocrine activation.