Scientist Navy Medical Research Center, Silver Spring
Abstract Text:
Background: Aeromedical evacuation (AE) is central to the current strategies employed for the timely transport of combat-related neurotrauma patients from theatre to definitive care. The AE environment exposes patients to hypobaric hypoxia, which has been shown to worsen clinical outcomes in neurotrauma in both animal models and retrospective review of patient data. The sustained activation of microglia, the immunomodulatory cells of the central nervous system, has been directly implicated in secondary injury and progressive cognitive decline following traumatic brain injury. This phenomenon has been shown to be exacerbated by exposure to hypobaria.
Methods: To better evaluate the effects of hypobaria on microglia, we exposed an immortalized microglial cell line (BV2) to a pressure of 8,000 ft with 25% reduction in oxygen for 4 hours, simulating an AE (SAE). Following a 72-hour recovery period, we used acridine orange propidium iodide (AOPI) stain to evaluate cellular viability and proliferation. Immunocytochemistry was also used to assess ionized calcium-binding adaptor protein-1 (IBA-1) as an indicator of microglial activation.
Results: There was a significant decrease in oxygen associated with cultures exposed to SAE as compared to normobaria. There did not appear to be a relationship between SAE and cellular viability or proliferation as assessed by AOPI staining. There were also no significant changes in morphology to include cell diameter, process number or length, as assessed by microscopy. Furthermore, there was no apparent increase in IBA-1.
Conclusions: Hypobaric hypoxia consistent with conditions experienced in a SAE environment, did not alter BV2 microglial viability, proliferation, morphology, or activation in early in vitro modeling. Understanding the relationship of microglial dysfunction to secondary injury and cognitive dysfunction following neurotrauma and well as the associated mechanisms, will address a key knowledge gap in the AE literature and better inform management. Future studies are needed to further evaluate the effect of supplemental oxygen as well as manipulations of the degree of hypobaria, duration of exposure, and the effect of multiple exposures.
