Mild traumatic brain injury (mTBI) in a murine model increases survival to a bacterial pulmonary challenge compared with blunt tail trauma (TT). We hypothesize substance P and its receptor, the neurokinin 1 receptor (NK1R; official name TACR1), play a role in the increased survival of mTBI mice. Mice were subjected to mTBI or TT, and 48 hours after trauma, the levels of NK1R mRNA and protein were significantly up-regulated in mTBI lungs. Examination of the lung 48 hours after injury by microarray showed significant differences in the expression of 433 gene sets between groups, most notably genes related to intercellular proteins. Despite down-regulated gene expression of connective proteins, the presence of an intact pulmonary vasculature was supported by normal histology and bronchoalveolar lavage protein levels. To determine whether these mTBI-induced lung changes benefited in vivo responses, two chemotactic stimuli (a CXCL1 chemokine and a live Pseudomonas aeruginosa infection) were administered 48 hours after trauma. For both stimuli, mTBI mice recruited more neutrophils to the lung 4 hours after instillation (CXCL1: mTBI = 6.3 ± 1.3 versus TT = 3.3 ± 0.7 neutrophils/mL; Pseudomonas aeruginosa: mTBI = 9.4 ± 1.4 versus TT = 5.3 ± 1.1 neutrophils/mL). This study demonstrates that the downstream consequences of mTBI on lung NK1R levels and connective protein expression enhance neutrophil recruitment to a stimulus that may contribute to increased survival.
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