Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Toward a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

Stephen Thomas Ahlers,Debra Ann Shear,Michael Christopher Shaughness,James Radford Stone,Richard Michael Mccarron,Elaina Vasserman-Stokes,Mikulas Chavko,Aaron Andrew Hall

doi:10.3389/fneur.2012.00032

Stephen Thomas Ahlers, Debra Ann Shear + Show 6 more

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https://doi.org/10.3389/fneur.2012.00032

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Abstract

Mild traumatic brain injury (mTBI) resulting from exposure to improvised explosive devices (IEDs) has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP). En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations) to 36.6, 74.5, and 116.7 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 116.7 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 116.7 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 116.7 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 74.5 kPa facing the BOP wave and rats exposed to 116.7 kPa in the lateral (side) orientation. We next assessed repeated exposure to either lateral or frontal 36.6 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of long-term brain injury from blast exposure.

Highlights

Significant attention has been focused on mild traumatic brain injury resulting from exposure to improvised explosive devices (IEDs; Okie, 2005; Warden and French, 2005; Warden, 2006; Hicks et al, 2010; Moore and Jaffee, 2010; Peskind et al, 2010; Snell and Halter, 2010)
ACUTE blast overpressure (BOP) EXPOSURE Balance beam task Figures 1A–C depict the effects of exposure to 36.6, 74.5, and 116.7 kPa BOP, respectively, in rats performing on the balance beam task
Performance in 36.6 and 74.5 kPa conditions showed no significant deviation of beam walking ability regardless of the time assessed after BOP exposure or orientation to the BOP wave

Summary

Introduction

Significant attention has been focused on mild traumatic brain injury (mTBI) resulting from exposure to improvised explosive devices (IEDs; Okie, 2005; Warden and French, 2005; Warden, 2006; Hicks et al, 2010; Moore and Jaffee, 2010; Peskind et al, 2010; Snell and Halter, 2010). Studies of mTBI resulting from blast exposure occur within a broader context to understand the relationship between brain injury and blast exposures across the TBI spectrum (mild, moderate, and severe), with the aim to characterize underlying pathophysiological mechanisms and consequent neurological impairments. Freedom are mild and are presumed to result from one or more exposures to IEDs. IEDs produce moderate and severe TBI that is often a component of polytrauma involving amputations, organ damage, and overwhelming systemic injury (Zouris et al, 2006; Bell et al, 2009). The conditions of blast exposure that produce mTBI in humans are not well understood This is in part due to the complexity of the combat environment, with many IED exposures involving some combination of blast overpressure (BOP) exposure, blunt impact, and/or acceleration/deceleration inertial loading. Connecting a clinical diagnosis of mTBI to single or multiple traumatic exposures is further complicated by the subtle nature of the injury, concerns over adequate diagnostic criteria www.frontiersin.org

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