Pulmonary injury risk curves and behavioral changes from blast overpressure exposures of varying frequency and intensity in rats

Abstract

At present, there are no set guidelines establishing cumulative limits for blast exposure numbers and intensities in military personnel, in combat or training operations. The objective of the current study was to define lung injury, pathology, and associated behavioral changes from primary repeated blast lung injury under appropriate exposure conditions and combinations (i.e. blast overpressure (BOP) intensity and exposure frequency) using an advanced blast simulator. Male Sprague Dawley rats were exposed to BOP frontally and laterally at a pressure range of ~ 8.5–19 psi, for up to 30 daily exposures. The extent of lung injury was identified at 24 h following BOP by assessing the extent of surface hemorrhage/contusion, Hematoxylin and Eosin staining, and behavioral deficits with open field activity. Lung injury was mathematically modeled to define the military standard 1% lung injury threshold. Significant levels of histiocytosis and inflammation were observed in pressures ≥ 10 psi and orientation effects were observed at pressures ≥ 13 psi. Experimental data demonstrated ~ 8.5 psi is the threshold for hemorrhage/contusion, up to 30 exposures. Modeling the data predicted injury risk up to 50 exposures with intensity thresholds at 8 psi for front exposure and 6psi for side exposures, which needs to be validated further.

Repeated Low-Level Blast Acutely Alters Brain Cytokines, Neurovascular Proteins, Mechanotransduction, and Neurodegenerative Markers in a Rat Model

“…Together, these data indicate that repeated daily exposure to low-level BOP has significant effects on the brain in the short term, and these effects may contribute to long-term deficits reported by Warfighters. Importantly, the low intensities of BOP studied here do not cause gross lung injury (Sajja et al, 2020), so these effects are likely due to the direct effects of BOP on the brain rather than as the indirect result of systemic injuries.…”

“…The pressure data was recorded at 800,000 samples/s that is baselined to ambient pressure with TMX 18 data recorder (Astronova, West Warwick, RI, USA). To avoid poly-organ injury in these experiments, acetate membranes (Grafix Inc., Ohio, OH, USA) were used to yield peak positive static pressures of 8.5 psig (positive pressure-impulse: 11.46 psig * ms, duration: 2.94 ms; negative pressure-impulse: −8.35 psig * ms, peak: −2.86 psig, duration: 5.89 ms) or 10 psig (positive pressure-impulse: 16.64 psig * ms, duration: 4.0 ms; negative pressure-impulse: −10.27 psig * ms, peak: −2.34 psig, duration: 7.07 ms) with a positive phase duration of 3-5 ms) as in Sajja et al (2020). Pressure profiles are shown in Figure 1.…”

“…Contrary to impact TBI, BOP exposure causes complex, whole-body injury, with air-filled organs such as the lungs and ears being particularly vulnerable (Sajja et al, 2020). Several studies have shown brain perturbations in the form of the disrupted blood-brain barrier (BBB) and increased brain permeability following BOP exposure (Rubovitch et al, 2012;Elder et al, 2015).…”

“…To develop BOP injury risk criteria for brain and lungs, our group has evaluated poly-organ trauma as evidenced by lung and brain injuries and established that 8.5 psi is the threshold for lung contusion for up to 30 daily exposures and that multiple daily exposures to 10 psi BOP cause around 1% lung injury (Heyburn et al, 2019a;Sajja et al, 2020). To expand on these previous findings and to further develop head injury risk criteria associated with repeated low-level BOP exposure, several markers known to be altered in the brain from relatively high-intensity BOP exposure were evaluated in the absence of lung injury.…”

Blast Waves Cause Immune System Dysfunction and Transient Bone Marrow Failure in a Mouse Model

“…However, its effects on the body can last for long after exposure and involve interlinked mechanisms of systemic, local and cerebral responses. It has been well documented that BW exposure leads to air embolism ( Kirkman and Watts, 2011 ; van H. Mason et al, 1971 ), activation of the autonomic nervous system (ANS) ( Cernak et al, 1996 ; Tümer et al, 2013 ), compromised blood flow throughout the body ( Health, 2014 ), blood brain barrier disruption ( Kuriakose et al, 2018 ), systemic inflammation ( Surbatovic et al, 2007 ; Cernak, 2010 ), along with damage to the lungs ( Elsayed and Gorbunov, 2007 ; Koliatsos et al, 2011 ; Sajja et al, 2020 ) and intestines ( Cripps and Cooper, 1997 ; Bala et al, 2008 ). As the BW propagates through the entire body and all the tissues, it triggers numerous biochemical and physiological changes, such as the release of reactive oxygen species (ROS) and subsequent damage to proteins ( Cho et al, 2013 ), damage associated molecular patterns (DAMPs) released from necrotic cells, general tissue hypoxia due to compromised blood flow, and immunological changes both locally and systemically ( Thompson et al, 2019 ).…”