Low-Intensity Blast Exposure Induces Multifaceted Long-Lasting Anxiety-Related Behaviors in Mice.

Abstract

Primary blast exposure is a predominant cause of mild traumatic brain injury (mTBI) among veterans and active-duty military personnel, and affected individuals may develop long-lasting behavioral disturbances that interfere with quality of life. Our prior research with the "Missouri Blast" model demonstrated behavioral changes relevant to deficits in cognitive and affective domains after exposure to low-intensity blast (LIB). In this study, behavioral evaluations were extended to 3 months post-LIB injury using multifaceted conventional and advanced behavioral paradigms. C57BL/6J male mice, aged 2 months old, were subjected to a non-inertial primary LIB-induced mTBI by detonating 350 g of C-4 at a 3-m distance on 1-m-tall platforms. Three months after injury, mice were evaluated using the open-field test (OFT), social interaction test, and advanced Erasmus Ladder paradigm. With OFT, no apparent anxiety-like changes were detected with the LIB-exposed mice and sham controls, and both groups displayed similar center-zone activities. Although no social interaction parameters reached significance, a majority of LIB-exposed mice initiated less than 50% of interactions compared with their interaction partners, suggesting decreased sociability. With the Erasmus Ladder test to assess motor functions, associative learning, and stimulus response, LIB-exposed mice appeared to display increased instances of leaving before the cue, reminiscent of "escape behavior," indicative of anxiety-related activity different from that OFT detected. Overall, these results revealed subtle multifaceted long-lasting anxiety-relevant effects following LIB exposure. The "Missouri Blast" platform offers a basis for future research to investigate the underlying biological mechanism(s) leading to domain-specific behavioral changes.