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

• Published in: Neuropharmacology 2019-02, Vol.145 (Pt B), p.220-229
• Main Authors: Perez-Garcia, Georgina, Gama Sosa, Miguel A., De Gasperi, Rita, Tschiffely, Anna E., McCarron, Richard M., Hof, Patrick R., Gandy, Sam, Ahlers, Stephen T., Elder, Gregory A.
• Format: Article
• Language: English
• Subjects: Animal models; Anxiety; BCI-838; Blast; Metabotropic glutamate receptor; Post-traumatic stress disorder; Postconcussion syndrome; Rat; Traumatic brain injury
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2018.09.023

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”. •Separating the effects of blast-related mTBI from PTSD has been difficult.•Blast exposure in rats induces PTSD-related traits without a psychogical stressor.•mGluR2/3 antagonists such as BCI-838 may treat the PTSD that follows blast injury.