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

J Neurotrauma. 2017 Jan 1;34(1):145-164. doi: 10.1089/neu.2015.4310. Epub 2016 Mar 30.

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.

Keywords: PTSD; animal model; blast-wave; mTBI.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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