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

• Published in: Journal of neurotrauma Vol. 34; no. 1; p. 145
• Main Authors: Zuckerman, Amitai, Ram, Omri, Ifergane, Gal, Matar, Michael A, Sagi, Ram, Ostfeld, Ishay, Hoffman, Jay R, Kaplan, Zeev, Sadot, Oren, Cohen, Hagit
• Format: Journal Article
• Language: English
• Published: United States 01-01-2017
• Subjects: Animals; Anxiety - diagnostic imaging; Anxiety - etiology; Anxiety - psychology; Blast Injuries - complications; Blast Injuries - diagnostic imaging; Blast Injuries - psychology; Brain Concussion - complications; Brain Concussion - diagnostic imaging; Brain Concussion - psychology; Comorbidity; Disease Models, Animal; Male; Maze Learning - physiology; Pressure - adverse effects; Random Allocation; Rats; Rats, Sprague-Dawley; Stress Disorders, Post-Traumatic - diagnostic imaging; Stress Disorders, Post-Traumatic - etiology; Stress Disorders, Post-Traumatic - psychology; PTSD; blast-wave; animal model; mTBI
• ISSN: 1557-9042
• DOI: 10.1089/neu.2015.4310

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.