title: Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury.
abstract: Aeromedical evacuation, an important component in the care of many patients with traumatic brain injury (TBI), particularly in war zones, exposes them to prolonged periods of hypobaria. The effects of such exposure on pathophysiological changes and outcome after TBI are largely unexplored. The objective of this study was to investigate whether prolonged hypobaria in rats subjected to TBI alters behavioral and histological outcomes. Adult male Sprague-Dawley rats underwent fluid percussion induced injury at 1.5-1.9 atmospheres of pressure. The effects of hypobaric exposure (6 h duration; equivalent to 0.75 atmospheres) at 6, 24, and 72 h, or 7 days after TBI were evaluated with regard to sensorimotor, cognitive, and histological changes. Additional groups were evaluated to determine the effects of two hypobaric exposures after TBI, representing primary simulated aeromedical evacuation (6 h duration at 24 h after injury) and secondary evacuation (10 h duration at 72 h after injury), as well as the effects of 100% inspired oxygen concentrations during simulated evacuation. Hypobaric exposure up to 7 days after injury significantly worsened cognitive deficits, hippocampal neuronal loss, and microglial/astrocyte activation in comparison with injured controls not exposed to hypobaria. Hyperoxia during hypobaric exposure or two exposures to prolonged hypobaric conditions further exacerbated spatial memory deficits. These findings indicate that exposure to prolonged hypobaria up to 7 days after TBI, even while maintaining physiological oxygen concentration, worsens long-term cognitive function and neuroinflammation. Multiple exposures or use of 100% oxygen further exacerbates these pathophysiological effects.
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Skovira
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Shruti V
authors.initials: SV
authors.lastname: Kabadi
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Zaorui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: 2 Program in Trauma, Center for the Sustainment of Trauma and Readiness Skills (C-STARS), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Joseph
authors.initials: J
authors.lastname: DuBose
authors.affiliation: 3 Department of Emergency Medicine, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Gary
authors.initials: G
authors.lastname: Fiskum
authors.affiliation: 1 Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D000399:Air Pressure; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D018496:Hyperoxia; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000502:physiology
keywords: aeromedical evacuation; hypobaria; inflammation; neuronal cell death; traumatic brain injury