Hypobaric Hypoxia Exacerbates the Neuroinflammatory Response to Traumatic Brain Injury

• Published in: The Journal of surgical research Vol. 165; no. 1; pp. 30 - 37
• Main Authors: Goodman, Michael D., M.D, Makley, Amy T., M.D, Huber, Nathan L., M.D, Clarke, Callisia N., M.D, Friend, Lou Ann W, Schuster, Rebecca M, Bailey, Stephanie R, Barnes, Stephen L., M.D, Dorlac, Warren C., M.D, Johannigman, Jay A., M.D, Lentsch, Alex B., Ph.D, Pritts, Timothy A., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2011; Elsevier
• Subjects: Adult and adolescent clinical studies; aeromedical evacuation; Animals; Biological and medical sciences; Brain Injuries - immunology; Chemokine CCL3 - blood; General aspects; hypobaric; hypoxia; Hypoxia - complications; inflammation; Inflammation - etiology; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin-6 - blood; Male; Medical sciences; Mice; Mice, Inbred C57BL; neuroinflammation; Organic mental disorders. Neuropsychology; Phosphopyruvate Hydratase - blood; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reflex, Righting; Surgery; Traumas. Diseases due to physical agents; traumatic brain injury; traumatic brain injury; hypoxia; aeromedical evacuation; hypobaric; inflammation; neuroinflammation; Nervous system diseases; Oxygen; Inflammation; Medicine; Treatment; Surgery; Evacuation; Hypoxia; Head trauma
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.05.055

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.