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

Amitai Zuckerman, Omri Ram, Gal Ifergane, Michael A. Matar, Ram Sagi, Ishay Ostfeld, Jay R. Hoffman, Zeev Kaplan, Oren Sadot, Hagit Cohen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish
Pages (from-to)145-164
Number of pages20
JournalJournal of Neurotrauma
Volume34
Issue number1
DOIs
StatePublished - 1 Jan 2017

Keywords

  • PTSD
  • animal model
  • blast-wave
  • mTBI

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