title: Hypobaric hypoxia exacerbates the neuroinflammatory response to traumatic brain injury.
abstract: OBJECTIVE
  To determine the inflammatory effects of time-dependent exposure to the hypobaric environment of simulated aeromedical evacuation following traumatic brain injury (TBI).
  
  
  METHODS
  Mice were subjected to a blunt TBI or sham injury. Righting reflex response (RRR) time was assessed as an indicator of neurologic recovery. Three or 24 h (Early and Delayed groups, respectively) after TBI, mice were exposed to hypobaric flight conditions (Fly) or ground-level control (No Fly) for 5 h. Arterial blood gas samples were obtained from all groups during simulated flight. Serum and cortical brain samples were analyzed for inflammatory cytokines after flight. Neuron specific enolase (NSE) was measured as a serum biomarker of TBI severity.
  
  
  RESULTS
  TBI resulted in prolonged RRR time compared with sham injury. After TBI alone, serum levels of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC) were increased by 6 h post-injury. Simulated flight significantly reduced arterial oxygen saturation levels in the Fly group. Post-injury altitude exposure increased cerebral levels of IL-6 and macrophage inflammatory protein-1α (MIP-1α), as well as serum NSE in the Early but not Delayed Flight group compared to ground-level controls.
  
  
  CONCLUSIONS
  The hypobaric environment of aeromedical evacuation results in significant hypoxia. Early, but not delayed, exposure to a hypobaric environment following TBI increases the neuroinflammatory response to injury and the severity of secondary brain injury. Optimization of the post-injury time to fly using serum cytokine and biomarker levels may reduce the potential secondary cerebral injury induced by aeromedical evacuation.
authors.affiliation: Institute for Military Medicine, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. goodmamd@uc.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Goodman
authors.forename: Amy T
authors.initials: AT
authors.lastname: Makley
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Huber
authors.forename: Callisia N
authors.initials: CN
authors.lastname: Clarke
authors.forename: Lou Ann W
authors.initials: LA
authors.lastname: Friend
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Schuster
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Bailey
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Barnes
authors.forename: Warren C
authors.initials: WC
authors.lastname: Dorlac
authors.forename: Jay A
authors.initials: JA
authors.lastname: Johannigman
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000276:immunology*; D054405:Chemokine CCL3 / Q000097:blood; D000860:Hypoxia / Q000150:complications*; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010751:Phosphopyruvate Hydratase / Q000097:blood; D057897:Reflex, Righting
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D015850:Interleukin-6; D010751:Phosphopyruvate Hydratase