- The intense focus in the clinical literature on the mental and neuro-cognitive sequelae of explosive blast-wave exposure, especially when they co-morbid 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 non-anesthetized 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 bio-behavioral 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 groups 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. This experimental animal model can be a useful tool to elucidate neurobiological mechanisms underlying the effects of blast wave-induced mTBI and PTSD and comorbid mTBI-PTSD.