Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury–Post-Traumatic Stress Disorder

Abstract

The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

Behavioral and inflammatory response in animals exposed to a low-pressure blast wave and supplemented with β-alanine

“…The overpressure wave is followed with a negative pressure wave that is sustained for more than 0.66 ms with a peak negative pressure of −40 kPa (−5.8 psi). This blast protocol is reported to result in a sound pressure level of 193 dB and a light intensity of approximately 5 Mlux (Zuckerman et al 2016), which is similar to that experienced during exposure to a M84 stun grenade at a distance of 1.5 m (3.1 Mlux). The peak overpressure deviations between the different experimental trials were between 1 and 3%.…”

“…Non-anesthetized rats were subjected to a single blast wave with the head facing the blast without any body shielding, resulting in a full body exposure to the blast wave. Previous research has reported that this low-pressure blast wave results in a mean peak overpressure of 95 kPa (13.77 psi) (rise time of 0.01 ms) that is sustained for a duration of 0.19 ms and leads to a peak impulse of 10.8 × 10 −3  kPa s −1 (Zuckerman et al 2016). The overpressure wave is followed with a negative pressure wave that is sustained for more than 0.66 ms with a peak negative pressure of −40 kPa (−5.8 psi).…”

“…In an actual explosion the blast wave causes an acute, short-duration elevation in pressure followed by a negative phase. The exploding wire system has been shown to be capable of simulating this overpressure and negative pressure blast wave profile (Ram and Sadot 2012; Zuckerman et al 2016). …”

“…Following the blast rats were returned to their home cage. Exposure to this experimental blast wave has recently been validated to elicit distinct behavioral and morphological responses modelling mTBI-like, PTSD-like and comorbid mTBI-PTSD-like behaviors (Zuckerman et al 2016). …”

“…Diagnostic criteria that have been previously validated and proven to be reliable were used determine whether an animal exhibited mTBI behavior. Detailed discussion on the cognitive criteria used has been recently reported by Zuckerman et al (2016). Briefly, the experimental decay parameters, Y  =  Y 0  +  A / t , were calculated from the escape latency determined during the MWM for both acquisition and reversal phases. …”