Blast-induced "PTSD": Evidence from an animal model

  • Neuropharmacology. 2019 Feb;145(Pt B):220-229. doi: 10.1016/j.neuropharm.2018.09.023.
Georgina Perez-Garcia  1 ,  Miguel A Gama Sosa  2 ,  Rita De Gasperi  3 ,  Anna E Tschiffely  4 ,  Richard M McCarron  5 ,  Patrick R Hof  6 ,  Sam Gandy  7 ,  Stephen T Ahlers  4 ,  Gregory A Elder  8
Affiliations
  • 1. Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA.
  • 2. General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA.
  • 3. Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA.
  • 4. Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
  • 5. Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20914, USA.
  • 6. Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 7. Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA; Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; NFL Neurological Care Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 8. Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA; Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. Electronic address: [email protected].
PMID: 30227150 DOI: 10.1016/j.neuropharm.2018.09.023
Abstract

A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor. Rats exposed to repetitive low-level blasts consisting of three 74.5 kPa exposures delivered once daily for three consecutive days develop a variety of anxiety and PTSD-related behavioral traits that are present for at least 9 months after blast exposure. A single predator scent challenge delivered 8 months after the last blast exposure induces additional anxiety-related changes that are still present 45 days later. Because the blast injuries occur under general anesthesia, it appears that blast exposure in the absence of a psychological stressor can induce chronic PTSD-related traits. The reaction to a predator scent challenge delivered many months after blast exposure suggests that blast exposure in addition sensitizes the brain to react abnormally to subsequent psychological stressors. The development of PTSD-related behavioral traits in the absence of a psychological stressor suggests the existence of blast-induced "PTSD". Findings that PTSD-related behavioral traits can be reversed by BCI-838, a group II metabotropic glutamate receptor antagonist offers insight into pathogenesis and possible treatment options for blast-related brain injury. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

Keywords
Animal models; Anxiety; BCI-838; Blast; Metabotropic glutamate receptor; Post-traumatic stress disorder; Postconcussion syndrome; Rat; Traumatic brain injury.
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