Research Associate University of Maryland School of Medicine
Abstract Text:
Background: Under-vehicle blast (UVB) causes a unique traumatic brain injury (TBI) in warfighters targeted by improvised explosive devices. UVB hyper-acceleration can produce a TBI independent of impact, however, an impact injury can also occur. Previous studies in rats have shown that aeromedical evacuation-relevant hypobaria exposure within 72 hours of TBI exacerbates neurologic injury. While rat studies investigating TBI are useful, translating findings to improved patient outcomes is challenging, perhaps due to differences in cerebral architecture between humans and rodents. Thus, a model of UVB + impact TBI was developed in ferrets, who possess human-like gyrencephalic brains.
Methods: The protocol was reviewed and approved by the University of Maryland, Baltimore Institutional Animal Care and Use Committee (0620009) and the U.S. Air Force Surgeon General’s Office of Research Oversight and Compliance as protocol number FWR-2020-0015A. Animal activities were conducted in compliance with all federal regulations governing the protection of animals and research. In this study, adult male ferrets were sedated, secured to a metal plate “vehicle,” exposed to UVB via detonation of pentaerythritol tetranitrate, and then anesthetized and given a controlled cortical impact (BCCI). Twenty-four hours post-injury, animals underwent a 6-hour simulated aeromedical evacuation by exposing them to ambient pressures equivalent to those at 8000 ft (hypobaria; HB; 574 mmHg) or remained at sea level (normobaria; NB; 760 mmHg). Mood (play behavior) and motor function (ladder walk) were assessed monthly in BCCI and age-matched naïve animals. Additional tests examining mood and motor function (open field), as well as memory (novel object recognition and object location) were employed only once at six months post-injury.
Results and
Conclusions: Decreased time spent in the center zone of the open field apparatus suggests increased anxiety-like behavior in BCCI ferrets at 6 months post-injury, particularly in those exposed to hypobaria. Perirhinal cortex-dependent and, perhaps, hippocampus-dependent learning and memory may be impaired 6 months following BCCI+HB but not BCCI+NB. No significant differences were noted in play behavior though it is likely that repeated exposures of ferrets to assays of mood may decrease the sensitivity of the tests. Impairments in gross motor function/learning may persist for at least six months, however, injured animals do show improvement over time.
The preliminary results of this study indicate that ferrets have great potential as a gyrencephalic model for brain injury, allowing for the collection of rich neurobehavioral data. Experimentation for this project is ongoing and will, eventually, compare neurobehavioral outcomes from animals exposed to 0-5 simulated flights. Results will inform the creation of guidelines for the safe transport of TBI patients.
The views expressed are those of the authors and do not reflect the official guidance or position of the United States Government, the Department of Defense or of the United States Air Force. Supported by US Air Force FA8650-20-2-6H20.
Keywords: under-vehicle blast, controlled cortical impact, polytrauma, aeromedical evacuation, hypobaria, gyrencephalic, ferret, model, chronic, cognition, behavior, anxiety, memory, motor function
