title: 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.
authors.affiliation: 1 Faculty of Health Sciences, Ministry of Health, Anxiety and Stress Research Unit, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Amitai
authors.initials: A
authors.lastname: Zuckerman
authors.affiliation: 2 Department of Mechanical Engineering, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Omri
authors.initials: O
authors.lastname: Ram
authors.affiliation: 3 Headache Clinic, Department of Neurology, Soroka Medical Center, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Gal
authors.initials: G
authors.lastname: Ifergane
authors.affiliation: 1 Faculty of Health Sciences, Ministry of Health, Anxiety and Stress Research Unit, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matar
authors.affiliation: 4 Israel Defense Forces, Medical Corps , Tel-Aviv, Israel .
authors.forename: Ram
authors.initials: R
authors.lastname: Sagi
authors.affiliation: 4 Israel Defense Forces, Medical Corps , Tel-Aviv, Israel .
authors.forename: Ishay
authors.initials: I
authors.lastname: Ostfeld
authors.affiliation: 5 Institute of Exercise Physiology and Wellness, Sport and Exercise Science, University of Central Florida , Orlando, Florida.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Hoffman
authors.affiliation: 1 Faculty of Health Sciences, Ministry of Health, Anxiety and Stress Research Unit, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Zeev
authors.initials: Z
authors.lastname: Kaplan
authors.affiliation: 2 Department of Mechanical Engineering, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Oren
authors.initials: O
authors.lastname: Sadot
authors.affiliation: 1 Faculty of Health Sciences, Ministry of Health, Anxiety and Stress Research Unit, Ben-Gurion University of the Negev , Beer-Sheva, Israel .
authors.forename: Hagit
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001007:Anxiety / Q000000981:diagnostic imaging / Q000209:etiology / Q000523:psychology; D001753:Blast Injuries / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D001924:Brain Concussion / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D015897:Comorbidity; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011312:Pressure / Q000009:adverse effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging* / Q000209:etiology / Q000523:psychology
keywords: PTSD; animal model; blast-wave; mTBI